Subspeciality-Glaucoma
most anterior point of ciliary body the temporal scleral spur (Figure
to the perpendicular line from the 9).
inner wall of the sclera passing
through the scleral spur (Figure • Trabecular–Ciliary Angle (TCA)
14). is the angle between the posterior
corneal surface and the anterior
• Anterior Chamber Width (ACW) is surface of the ciliary body (Figure
the distance between the nasal and 11).
Figure 14: Ciliary body parameters on UBM such as Maximum Ciliary Body Thickness Figure 15: UBM showing angle in A: dark
(CBTmax), Ciliary Body Thickness at the distance of 1000 µm (CBT1000), Ciliary Body and B: light conditions. Further narrowing
Thickness at the scleral spur (CBT0), Anterior Placement of Ciliary Body (APCB) of the angle is seen in dark conditions with
the iris becoming more convex
UBM v/s Anterior segment Optical Coherence Tomography (ASOCT)
Principle UBM ASOCT
Based on low coherence interferometry
Based on high frequency (35–100 MHz range)
ultrasound waves
Method Contact scanning method Non-contact scanning method
Patient position Supine position Sitting position
Coupling medium Requires a silicone eyecup to hold a coupling No coupling medium required
medium like methylcellulose, normal saline etc
Patient compliance Required. Cannot be performed in uncooperative Easy to perform in uncooperative patients,
patients, children children
Time Time consuming Quicker
Risks Avoided in recently operated eyes due to risk of Safe to scan eyes with filtering blebs and recently
infection operated cases
Advantages Visualizes the structures behind the iris and Helps visualize anterior chamber angle clearly
tumor measurements
Structures behind Structures behind iris are clearly seen such as- Structures behind the iris are not seen clearly
iris plateau iris, angle-closure caused by iridociliary
cysts
Changes on various Useful for studying angle changes in light and Changes in angle on varying light conditions is
light conditions dark conditions (Figure 15) not well appreciated
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Subspeciality-Glaucoma
Various applications of UBM • Corneal and Scleral Diseases details. The lens status can also
in Ophthalmology (Figure 16-25) be assessed.
Specific instances where UBM has 3 The UBM is useful in opaque cor- 3 Depth of involvement in scleral
proved to be useful tool include the neas undergoing keratoplasty.2,3 and episcleral inflammation4 can
help in diagnosis and evaluating
following diseases: “Virtual gonioscopy” in these response to treatment.
instances gives an idea of angle
Figure 16: Corneal edema. The epithelium Figure 19: Adherent leucoma. Strands of iris Figure 22: Diffuse scleritis: Left arrow
layer is thickened loosing smooth and tissue extend anteriorly and are adherent to shows marked diffuse thickening of the
regular surface (white arrow). The stroma the posterior corneal surface. sclera, up arrow shows marked thinning of
also turns thickened appearing highly the remaining sclera
reflective.
Figure 20: The high reflectivity of the sclera
(arrows) allows it to be differentiated from
overlying and underlying tissue.
Figure 17: Descemet’s detachment: In cases Figure 23: In nodular scleritis, there is
of thickening of the cornea the desment’s nodular appearance of the sclera with ill-
detachment can be noted as a thin membrane defined margins
separate from corneal stroma
Figure 18: UBM of granular dystrophy. The Figure 21: Episcleritis. UBM reveals Figure 24: IOFB noted in the non-resolving
highly reflective hyaline bodies are outlined thickening of the episclera tissues (down scleral nodule with shadowing (left arrow)
against the stroma in the superficial cornea. arrow), but the stroma of sclera is not
affected (up arrow). A distinct border
was observed between scleral stroma
and episcleral tissues (including bulbar
conjunctiva and Tenon’s capsule)
52 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
origin and contents of the
cystic lesions of iris/ciliary body
and involvement of adjacent
structures and also distinguish it
from tumors.11,12
3 UBM by its ability to image both
surfaces of the iris can be useful
in assessing growth or regression
of the lesion on follow-up.
Figure 25: UBM of an eye with diffuse Figure 27: Loss of zonules and subluxation
scleritis shows mottled areas of lower of lens in an eye post blunt trauma. The
reflectivity in the sclera (arrow) with arrow marks the site of absent zonules and
thickened scleral layers. loss of iridolenticular contact
• Ocular Surface Tumors: With the 35 MHz probe it is also
Conjunctival and corneal surface possible to study the integrity of the
tumors5,6 can be assessed on UBM posterior capsule especially in cases
giving information regarding of traumatic cataract/posterior
the depth of tumor involvement, polar cataract.
involvement of adjacent and
intraocular structures and tumor • Intraocular Lens (IOL) Figure 29: Iris melanoma
Complications: Optic and haptic
residue/recurrence following locations can be assessed accurately
surgical excision. (Figure 26) by looking for a strong echo at their
interface plane. Most peripheral
portion of the haptic defines its
position in the capsular bag, ciliary
sulcus, or a dislocated IOL (Figure
28). The UBM is useful in studying
various other IOL complications
such as retained cortex or contact
of the IOL haptic with the iris or
ciliary body and thus, planning
management strategies.7-10
Figure 26: The UBM image of an eye with Figure 30: Ciliary Body cyst
clinical ocular surface squamous neoplasia
(OSSN) shows that the mass is homogenous,
low reflective, conjunctival and does not
involve the sclera/cornea
• Cataract Surgery Figure 28: Position of intraocular lens: Figure 31: Iris cyst with thin walls and
In cases of subluxation of the intraocular clear fluid inside
In cases with preoperative lens, the haptic position can be noted on
phacodonesis, area of zonular loss ultrasound biomicrosopy. Haptic is seen in
or altered tension will be seen on contact with ciliary processes
UBM. By imaging and measuring
the lens diameter and sulcus to • Anterior Segment Cystic Lesions
sulcus measurements one is able and Tumors (Figure 29-32):
to distinguish between various
causes of phacodonesis and plan 3 UBM helps to characterize the
IOL placement accordingly.
(Figure 27)
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Subspeciality-Glaucoma
Figure 32: UBM image showing central Figure 33: Ultrasound biomicroscopy of Figure 36: Angle recession usually occurs
iris lesions that usually produce a fusiform foreign body in the angle (arrow) shows in eye contusion. The UBM hallmark
thickening without iris bowing. high reflectivity and total shadowing of of the lesion is laceration of angle apex
structures behind it. (white arrow) with the ciliary body band
3 It helps differentiate between abnormally widened
a tumor and a cyst and also Figure 34: A case of cyclodialysis following
involvement of adjacent ciliary blunt trauma. Ultrasound biomicroscopy Figure 37: Ciliary body detachment in
body. shows that the ciliary body and iris root trauma is often led by suprachoroidal
(white arrow) are disinserted from the lumen hemorrhage or severe exudative
3 Demonstration of recurrence at scleral spur (black arrow) and moved 2 inflammation of choroidal vessels. The
the margins of the surgical site mm posteriorly. The peripheral iris is lying UBM manifestation is dark space between
after tumor excision is a function against the scleral spur. choroids and sclera (asterisk) with highly
of the UBM. reflective septum (white arrowhead) inside.
Figure 35: Ultrasound biomicroscopic Angle recession also occurred in this patient
3 Small ciliary body tumors as appearance of an iridodialysis. The iris is (black arrow)
well as cysts, which can mimic dis-inserted at the iris root.
tumors are best assessed on 3 Demonstration of angle sclera and ciliary body leading
UBM.13 to a direct communication
recession (Figure 36). In eyes between the anterior chamber
3 In case of larger tumors, UBM with angle recession, the ciliary and suprachoroidal space.
may be useful in defining the body face is torn at the iris • Vitreoretinal Surgery: The
limits of extension of the tumor. insertion, resulting in a wide- ability of the UBM to clearly
angle appearance whereas in image structural changes at the
3 The UBM is useful in defining the cyclodialysis there is disruption sclerotomies post pars plana
posterior extent of ciliary body of the interface in between the vitrectomy (PPV)18-20 has helped
tumors as well as the anterior to distinguish healing patterns
extent of peripheral choroidal and complications. It has greatly
tumors. helped in evaluating PPV
3 Anterior extent of tumors such
as retinoblastoma can also be
determined, permitting a more
accurate staging.14
• Trauma (Figure 33-37)
3 The UBM is useful in anterior
segment blunt and penetrating
trauma where media may be
opaque (due to corneal damage
and/or hyphema).
3 Demonstration of anterior
segment foreign bodies,15
3 Demonstration of cyclodialysis
clefts (Figure 9),16
3 Demonstration of zonular
damage17
54 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
related complications such as Figure 40: UBM of an eye with miotic pupil Figure 42: This UBM image-montage shows
anterior hyaloidal fibrovascular due to uveitis with active pars planitis. Note the effect of laser iridotomy. Angles have
proliferation and retinal break the low reflective exudative mass on ciliary opened after laser PI, and the bombe iris
formation and planning its processes and pars plana (arrow heads) (marked by white arrow in Fig. A) becomes
management. flat (shown as Fig. B). The iris insertion is
• Anterior segment Inflammation located in the middle of the anterior face of
and Hypotony (Figure 38-41): the ciliary body, suggesting the location of
Uveitic eyes very often have miotic iris insertion is important
pupils and hazy media making it
difficult to evaluate the posterior
segment. UBM helps in studying
the ciliary body and pars plana
in detail, identifying edema,
thickening, atrophy of ciliary
processes, cyclitic membranes, pars
plana exudates and membranes, as
well as ciliary body traction21-23 In
cases of unexplained hypotony,24
supraciliary effusion, ciliary body
membranes, causing traction or
atrophic ciliary processes can be
demonstrated each of which has
to be managed differently. UBM
is also helpful in evaluating cases
of recalcitrant uveitis such as that
caused by cilia or parasites.25,26
Figure 38: Ultrasound biomicroscopy of a Figure 41: Supraciliary effusion: Figure 43: Plateau Iris Syndrome showing
case with anterior uveitis showing pupillary Suparciliary effusion is noted at fluid in flat iris profile, angled iris root, anteriorly
block with iris bombe between the ciliary body and sclera (left rotated ciliary body and collapsed ciliary
Figure 39: Ciliary membranes: Pars planitis arrow) sulcus
or iridocyclitis may lead to formation of Figure 44: Phacomorphic Glaucoma-
cyclitic membranes (up arrow) Uses in glaucoma Enlarged anteroposterior diameter of lens
causing central iris elevation (as shown
• This is an area where extensive by arrows) & secondary angle closure
work has been done, using UBM.27 (pupillary block)
• The UBM has contributed
immensely to the understanding
of the behavior of the iris and
angle under various conditions
of illumination and the
pathogenesis of angle- closure
disease. (Figure 15)
• UBM can be used to find out
the mechanism of angle closure
which can occur at four anatomic
levels; the iris (pupillary block-
pre and post peripheral iridotomy
effect on angle- Figure 42), the
ciliary body (plateau iris in Figure
43), the lens (phacomorphic
glaucoma in Figure 44) and the
anterior vitreous face (malignant
glaucoma-Figure 45).
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Subspeciality-Glaucoma
effusion, which responds to and its patency can be verified in
medical management better, functioning blebs. Visualization
and another without effusion of intrascleral lakes of aqueous
that usually requires surgical following non penetrating filtering
management.30,31 (Figure 47) surgery and tube shunts in anterior
chamber is also possible. (Figure 49-
52)
Figure 45: Malignant glaucoma causing
anterior rotation of the iris-lens diaphragm
(up arrow)
3 The convex iris in pupillary
block shows flattening with
successful peripheral iridotomy. Figure 47: Flat anterior chamber (Thick
bold arrow) with anterior displacement
3 Poor response to peripheral of lens and ciliary effusion in an eye with
iridotomy may be due to the malignant glaucoma (Thin arrow). The
plateau iris configuration, where presence of ciliary effusion indicates the need
the anteriorly located ciliary for aggressive medical management.
processes block the ciliary
sulcus preventing the peripheral • In pigment dispersion syndrome Figure 49: Normal trabeculectomy: Normal
iris from falling back after there is reverse pupillary block trabeculectomy is seen on ultrasound
iridotomy.28 (Figure 46) where the posterior bowing of biomicrosopy well as it shows the tract (up
the iris causes an increase in iris- arrow) and iridectomy (down arrow)
lens contact and sometimes iris
zonular contact as well (Figure
48).32,33 Demonstration of the
latter and its reversal following
peripheral iridotomy makes UBM
an important diagnostic modality
and planning of management of
pigment dispersal glaucoma.
Figure 46: Typical anteriorly-rotated,
large ciliary body supports the peripheral
iris (black arrow in Fig. A), preventing
the peripheral iris moving backward after
laser iridotomy (shown in Fig. B). Anterior
location of the iris insertion also plays a role
in this mechanism
3 The UBM also has been able to
demonstrate anterior rotation of Figure 48: Pigment dispersion syndrome:
the ciliary processes to make a Posterior bowing of the iris (down arrow)
diagnosis of malignant glaucoma causing touch between iris and zonules, Figure 50: (a) Failed trabeculectomy
(Figure 45).29 causing pigment dispersion procedure. Ultrasound biomicroscopy
shows a patent opening (white arrow),
3 In addition, it has allowed but no space at the scleral dissection site
classification of malignant • Demonstration of failed and (black arrow), and no bleb; (b) Functioning
glaucoma into two groups thus functioning filtering blebs on trabeculectomy procedure. The opening into
helping in deciding the course
of management at an early UBM helps in analyzing results of the anterior chamber (arrow) is continuous
filtering surgery as well as causes for with a patent intrascleral pathway, and a
stage; one with supraciliary failure. The stoma can be visualized filtering bleb is present.
56 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Figure 51: Tenon’s cyst: An ill-defined cyst is 7. Possibility of causing injury to lens implantation after capsular tear:
noted in the region of the bleb with multiple cornea with the eyecup, while ultrasound biomicroscopy evaluation. J
internal echoes (down arrow) performing UBM. Cataract Refract Surg. 2001;27(9):1423-7.
Figure 52: Ahmad implant- The position of Conclusions 8. Pavlin CJ, Rootman D, Arshinoff S,
the tube is imaged in the anterior chamber Even though newer techniques such Harasiewicz K, Foster FS. Determination
(arrow). as ASOCT and Pentacam have the of haptic position of transsclerally
• Cyclophotocoagulation results added advantage of being noncontact fixated posterior chamber intraocular
with better resolution of anterior lenses by ultrasound biomicroscopy. J
in shrinkage and blunting of the structures, UBM still stands superior Cataract Refract Surg. 1993;19(5):573-7.
ciliary processes. This can be clearly because of the deeper penetration and
visualized on UBM.34 better visualization of ciliary body, 9. Pavlin CJ, Buys YM, Pathmanathan
Limitations zonules, and lens. The future prospect T. Imaging zonular abnormalities
1. Inability to visualize structures of three‑dimensional‑UBM imaging using ultrasound biomicroscopy. Arch
deeper than 4 mm system to generate volumetric images Ophthalmol. 1998;116(7):854-7.
2. Requirement of immersion of ocular structures, which is currently
technique and an experienced being developed, looks promising. 10. Piette S, Canlas OA, Tran HV, Ishikawa
operator to perform the scan H, Liebmann JM, Ritch R. Ultrasound
3. Inability to perform UBM on eyes References biomicroscopy in uveitis-glaucoma-
with an open corneal or scleral hyphema syndrome. Am J Ophthalmol.
wound 1. Dada T, Sihota R, Gadia R, Aggarwal 2002;133(6):839-41.
4. Requires contact, hence not useful A, Mandal S, Gupta V. Comparison of
in eyes with an open corneal or anterior segment optical coherence 11. Marigo FA, Esaki K, Finger PT,
scleral wound, infections, and tomography and ultrasound Ishikawa H, Greenfield DS, Liebmann
postoperative patients biomicroscopy for assessment of the JM et al. Differential diagnosis of
5. Need for the patient to lie in supine anterior segment. J Cataract Refract anterior segment cysts by ultrasound
position while performing the scan Surg. 2007;33(5):837-40. biomicroscopy. Ophthalmology. 1999;
6. Difficulty to perform UBM in 106 (11):2131-5.
children 2. Dada T, Aggarwal A, Vanathi M, Gadia
R, Panda A, Gupta V, et al. Ultrasound 12 Bianciotto C, Shields CL, Guzman JM,
biomicroscopy in opaque grafts with Romanelli-Gobbi M, Mazzuca D Jr,
post-penetrating keratoplasty glaucoma. Green WR, et al. Assessment of anterior
Cornea. 2008;27(4):402-5. segment tumors with ultrasound
biomicroscopy versus anterior segment
3. Madhavan C, Basti S, Naduvilath TJ, optical coherence tomography in 200
Sangwan VS. Use of Ultrasound cases. Ophthalmology. 2011;118(7):1297-
Biomicroscopic Evaluation in 302.
Preoperative Planning of Penetrating
Keratoplasty. Cornea. 2000;19(1):17-21. 13. Marigo FA, Finger PT, McCormick SA,
Iezzi R, Esaki K, Ishikawa H, et al. Iris
4. Heiligenhaus A, Schilling M, Lung E, and ciliary body melanomas: ultrasound
Steuhl KP. Ultrasound biomicroscopy biomicroscopy with histopathologic
in scleritis. Ophthalmology. 1998;105 correlation. Arch Ophthalmol. 2000;
(3):527-34. 118(11):1515-21.
5. Ho VH, Prager TC, Diwan H, Prieto V, 14. Maberly DA, Pavlin CJ, McGowan HD,
Esmaeli B. Ultrasound biomicroscopy Foster FS, Simpson ER. Ultrasound
for estimation of tumor thickness biomicroscopic imaging of the
for conjunctival melanoma. J Clin anterior aspect of peripheral choroidal
Ultrasound. 2007;35(9):533-7. melanomas. Am J Ophthalmol.
1997;123(4):506-14.
6. Bianciotto C, Shields CL, Guzman JM,
Romanelli-Gobbi M, Mazzuca D Jr, 15. Deramo VA, Shah GK, Baumal CR,
Green WR, et al. Assessment of anterior Fineman MS, Corrêa ZM, Benson WE,
segment tumors with ultrasound et al. Ultrasound biomicroscopy as a
biomicroscopy versus anterior segment tool for detecting and localizing occult
optical coherence tomography in 200 foreign bodies after ocular trauma.
cases. Ophthalmology. 2011;118(7):1297- Ophthalmology. 1999;106(2):301-5.
302.
16. Gentile RC, Pavlin CJ, Liebmann JM,
7. Loya N, Lichter H, Barash D, Goldenberg- Easterbrook M, Tello C, Foster FS, et al.
Cohen N, Strassmann E, Weinberger Diagnosis of traumatic cyclodialysis by
D. Posterior chamber intraocular ultrasound biomicroscopy. Ophthalmic
Surg Lasers. 1996;27(2):97-105.
17. McWhae JA, Crichton AC, Rinke
M. Ultrasound biomicroscopy for
www.dosonline.org/dos-times DOS Times - Volume 26, Number 4, January-February 2021 57
Subspeciality-Glaucoma
the assessment of zonules after formation in uveitis. Br J Ophthalmol. 31. Liebmann JM, Weinreb RN, Ritch R.
ocular trauma. Ophthalmology. 1996;80(10):895-9. Angle-closure glaucoma associated with
2003;110(7):1340-3. occult annular ciliary body detachment.
24. Roters S, Szurman P, Engels BF, Bartz- Arch Ophthalmol. 1998;116(6):731-5.
18. Bhende M, Agraharam SG, Gopal L, Schmidt KU, Krieglstein GK. Ultrasound
Sumasri K, Sukumar B, George J, et al. biomicroscopy in chronic ocular 32. Potash SD, Tello C, Liebmann J, Ritch R.
Ultrasound biomicroscopy of sclerotomy hypotony: its impact on diagnosis and Ultrasound biomicroscopy in pigment
sites after pars plana vitrectomy management. Retina. 2002;22(5):581-8. dispersion syndrome. Ophthalmology.
for diabetic vitreous hemorrhage. 1994;101(2):332-9.
Ophthalmology. 2000;107(9):1729-36. 25. Bhende M, Biswas J, Gopal L. Ultrasound
biomicroscopy in the diagnosis 33. Carassa RG, Bettin P, Fiori M, Brancato
19. Kwok AK, Tham CC, Loo AV, Fan DS, and management of intraocular R. Nd:YAG laser iridotomy in pigment
Lam DS. Ultrasound biomicroscopy gnathostomiasis. Am J Ophthalmol. dispersion syndrome: an ultrasound
of conventional and sutureless pars 2005;140(1):140-2. biomicroscopic study. Br J Ophthalmol.
plana sclerotomies: a comparative and 1998;82(2):150-3.
longitudinal study. Am J Ophthalmol. 26. Bhende M, Biswas J, Sharma T, Chopra
2001;132(2):172-7. SK, Gopal L, Shroff CM. Ultrasound 34. Brancato R, Carassa RG. Value of
biomicroscopy in the diagnosis and ultrasound biomicroscopy for
20. Gutfleisch M, Dietzel M, Heimes B, management of pars planitis caused ciliodestructive procedures. Curr Opin
Spital G, Pauleikhoff D, Lommatzsch A. by caterpillar hairs. Am J Ophthalmol. Ophthalmol. 1996;7(2):87-92.
Ultrasound biomicroscopic findings of 2000;130(1):125-6.
conventional and sutureless sclerotomy Corresponding Author:
sites after 20-, 23-, and 25-G pars plana 27. Dada T, Gadia R, Sharma A, Ichhpujani
vitrectomy. Eye (Lond). 2010;24(7):1268- P, Bali SJ, Bhartiya S, et al. Ultrasound Dr Kanika Jain
72. biomicroscopy in glaucoma. Surv MS, DNB Ophthalmology, Senior Resident
Ophthalmol. 2011;56(5):433-50. Department of Ophthalmology
21. Tran VT, LeHoang P, Herbort CP. Deen Dayal Upadhyay Hospital, Hari Nagar,
Value of high frequency ultrasound 28. Pavlin CJ, Ritch R, Foster FS. Ultrasound Delhi
biomicroscopy in uveitis. Eye (Lond). biomicroscopy in plateau iris syndrome.
2001;15(1):23-30. Am J Ophthalmol. 1992;113(4):390-5.
23. Haring G, Nolle B, Wiechens B. 29. Trope GE, Pavlin CJ, Bau A, Baumal CR,
Ultrasound biomicroscopic imaging in Foster FS. Malignant glaucoma. Clinical
intermediate uveitis. Br J Ophthalmol. and ultrasound biomicroscopic features.
1998;82(6): 625-9. Ophthalmology. 1994;101(6):1030-5.
23. Gentile RC, Liebmann JM, Tello C, 30. Wang N, Zhou W, Ouyang J, Chen X, Wu
Stegman Z, Weissman SS, Ritch R. J. Pathogenesis and clinical classification
Ciliary body enlargement and cyst of the malignant glaucoma. Yan Ke Xue
Bao. 1999;15(4):238-41.
58 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Developmental Glaucoma
Sushmita Kaushik, MS, Savleen Kaur, MS, Surinder Singh Pandav, MD
Advanced Eye Centre, Postgraduate Institute of Medical Education and Research,
Chandigarh, India
Childhood glaucoma recognition began Primary childhood glaucoma
with the term buphthalmos, or ox- IA. Primary Congenital Glaucoma (PCG)
eyed, which was used to describe the 1. Isolated angle anomalies (+/ - mild congenital iris anomalies)
secondary effect of elevated intraocular 2. Meets glaucoma definition (usually with ocular enlargement)
pressure (IOP) on the elastic infantile 3. Subcategories based on age of onset
eye.1 Buphthalmos was subdivided into
simple buphthalmos due to a primary a. Neonatal or newborn onset (0-1 month)
mechanism, now known as primary b. Infantile onset (>1-24 months)
congenital glaucoma, and buphthalmos c. Juvenile onset or late-recognized (>2 years)
associated with other developmental 4. Spontaneously arrested cases with normal IOP but typical signs of PCG may be
anomalies. The more complex anatomic classified as PCG
classification was given by Hoskins,
which divided the developmental IB. Juvenile Open Angle Glaucoma (JOAG)
abnormalities into trabecular 1. No ocular enlargement
meshwork, iris, and/or cornea.2 The 2. No congenital ocular anomalies or syndromes
Shaffer-Weiss classification introduced 3. Open angle (normal appearance)
the categories of isolated congenital 4. Meets glaucoma definition
(infantile) glaucoma, glaucomas
associated with congenital anomalies, Secondary childhood glaucoma
and acquired glaucoma.3 Walton A: Glaucoma Associated with Non-Acquired Ocular Anomalies
proposed an exhaustive listing of all
disorders known to be associated with Includes conditions of predominantly ocular anomalies present at birth which
childhood glaucoma.4 may or may not be associated with systemic signs and meets glaucoma definition
Unlike the adult definition of glaucoma Includes:
which focuses on the pathology of • Axenfeld Rieger anomaly (syndrome if systemic associations)
the optic nerve to make the diagnosis, • Peters anomaly (Syndrome if systemic associations)
subdividing glaucoma in children is • Ectropion uveae; Congenital iris hypoplasia
more difficult because the optic nerve • Aniridia
can be difficult to evaluate properly in • Persistent fetal vasculature/PFV (if glaucoma present before cataract surgery)
the presence of corneal opacity. • Oculodermal melanocytosis (nevus of Ota)
The definition of childhood glaucoma • Posterior polymorphous dystrophy
is IOP-related damage to the eye, rather • Microphthalmos
than being based solely on optic-nerve • Microcornea
criteria as suggested by an expert panel • Ectopia lentis
of glaucoma specialists in the world. • Ectopia lentis et pupillae
The childhood glaucoma research
network (CGRN) composed of clinicians B: Glaucoma Associated with Non-Acquired Systemic Disease or Syndrome
and scientists who specialize in treating Includes conditions predominantly of systemic disease present at birth which
children with glaucoma, has provided a may be associated with ocular signs and meets the definition of glaucoma
new classification system of paediatric
glaucoma’s which is as follows5: C. Glaucoma Associated with Acquired Condition
D. Glaucoma Following Congenital Cataract Surgery
Meets glaucoma definition after cataract surgery performed
Excludes acquired cataract or cataract in the setting of a syndrome with a known
glaucoma relationship, such as Lowe syndrome, congenital rubella syndrome,
aniridia, or persistent fetal vasculature.
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Subspeciality-Glaucoma
Figure 1: An algorithm for classification of childhood glaucoma Most cases of primary congenital
glaucoma occur sporadically, but
Some commonly occurring there are no symptoms, glaucoma in in approximately 10% of cases, an
Developmental glaucomas are children does present with symptoms autosomal recessive hereditary pattern
described in more detail: and signs which can be detected is evident.4 The PCG gene has been
by pediatricians and even parents, mapped to three different genetic loci:
Primary Congenital Glaucoma who are usually the first contacts of GLC3A (2p21), GLC3B (1p36); and
Primary congenital glaucoma (PCG) is a these children. Primary congenital GLC3C (14Q24.3).5-7 The first gene to be
potentially blinding disease of children, glaucoma classically presents with a implicated in the pathogenesis of PCG
which if untreated, would result in triad of photophobia, epiphora and was the human cytochrome P450 gene
a lifetime of blindness. It occurs due blepharospasm. Many children in (CYP1B1).5 The involvement of CYP1B1
to obstruction of the drainage of the India present with corneal edema varies from 20% in Indonesians8 and
aqueous humor caused by a primary initially, without buphthalmos or Japanese9, to 50% among Brazilians,10
developmental anomaly at the angle of any of the classical signs. Conversely, and nearly 100% among Saudi
the anterior chamber. The onset of the many children may have had Arabians11 and Slovakian Gypsies12. In a
disease is in the neonatal or infantile symptoms for a considerable period study involving South Indian patients,
period, and is manifested by symptoms of time, before presentation to an 30.8 % of 138 PCG cases were found to
of raised IOP and corneal edema such ophthalmologist simply because the be positive for one of six mutations of
as excessive tearing, photophobia, disease was not thought of, hence the CYP1B1 gene.13 Ethnic differences
and an enlargement of the globe delaying diagnosis. and geographical variations may be
(buphthalmos). The consequences of associated with different mutation
persistently raised intraocular pressure Although primary congenital glaucoma patterns.
on the optic nerve are far more serious, is the most common glaucoma seen Most studies on the molecular biology
manifesting as axonal damage and in infancy, it is still an uncommon of PCG have investigated only the
eventual irreversible blindness. disease. In India, the incidence has coding region of the gene, though it
been reported to be 1: 3300 live births,3 is known that mutations in the non-
For any disease to be detected in which, with an annual birth rate of 25 coding regions could lead to changes
time, it is important for the signs million, translates to nearly 7,600 new in gene expression or splicing, which
and symptoms to be recognized. cases per year. The variable incidence in in turn have the potential to alter gene
Unlike glaucoma in adults, which is various ethnic groups point towards a function. Descriptions of causative
notoriously difficult to detect since genetic basis for the disease. mutations of PCG in the North
Indian population have also not been
published so far. In an ongoing study we
plan to investigate the entire CYP1B1
gene (including the non-coding region)
in North Indian patients with PCG, in
order to find molecular information on
PCG in this patient population, which
is ethnically distinct from the South
Indian population.
Epidemiology
This condition is now recognized
worldwide, but the incidence of the
disease varies substantially in different
ethnic groups from 1 in 1250 births
in Slovakian Roms1 to 1: 20,000 in
Scandinavian regions.16 In the West,
the average incidence is about 1 in
10,000 births,2 but appears to be higher
in Asians. In Saudi Arabia, it is reported
to be 1: 2500,11 while Indian data from
Andhra Pradesh have indicated an
incidence of 1: 3300,3 and the disease
60 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
was responsible for 4.2% of blindness of congenital glaucoma in a relatively CYP1B1 and PCG
in the pediatric population. small gypsy subpopulation of Slovakia.
In 1997, Stoilov et al28 reported
Inheritance The universalvalidity of the autosomal- that the cytochrome P4501B1 gene
recessive model has been challenged (CYP1B1; OMIM 601771) located
Most cases of PCG are sporadic in by reports of disease transmission within the GLC3A locus is mutated in
occurrence. However, the possible in successive generations, unequal individuals with PCG. Extensive allelic
genetic basis of the disease was sex distribution among the affected heterogeneity has been identified
recognized as far back as 1836, when it individuals, and a lower-than-expected in more than 25 separate CYP1B1
was noted to occur endemically in the number of affected siblings in the mutations segregating with the disease
Jewish population in Algiers.17 This familial cases. These observations phenotype.29-31 In studies involving
was followed by the documentation have raised the possibility that PCG is families of Turkey and Saudi Arabia
of a Swedish family18 in which seven a genetically heterogeneous disorder. and in Romany Slovakians, CYP1B1
brothers were affected by congenital The first molecular evidence for this mutations were observed in 90% to
glaucoma and the parents and possibility came from the genetic 100% of the studied families. Reduced
sisters were normal. Waardenburg19 linkage studies by identifying two penetrance was reported in the Saudi
suggested that recessive inheritance separate genetic loci associated with Arabian families with PCG,11 which
of some cases of glaucoma is proved the disease, thus confirming that PCG was attributed to the existence of
by (1) a high frequency of parental is indeed genetically heterogeneous.7 a dominant modifier locus that is
consanguinity; (2) the presence of Most of the PCG families were linked located on 8p. In ethnically mixed
the disease in about 25% of sibs of to the GLC3A locus on 2p21. However, populations, mutations were found in
probands; (3) the presence of the few other families were linked to the 20–30% of patients with PCG, whereas
disease in all children of a marriage GLC3B locus on 1p36. The existence in consanguineous populations the
between 2 affected persons; and (4) the of linkage between the GLC3A locus prevalence increases to 85%.32
occurrence of glaucoma in collaterals and PCG phenotype was subsequently
of both parents in some families. confirmed in PCG families from Saudi Structural defects and
Arabia and Romany Slovakians.
In approximately 10% of cases in Clinical Features
which a hereditary pattern is evident, Demenais et al24 confirmed genetic
inheritance is usually believed to be heterogeneity of congenital glaucoma. The glaucomas are a heterogeneous
autosomal recessive with variable An analysis by Morton25 suggested that group of insidious diseases associated
penetrance.7 Beiguelman and Prado20 much etiologic heterogeneity exists with elevated intraocular pressure
reported a Brazilian pedigree as in congenital glaucoma. A large gypsy (IOP) and optic nerve atrophy. Primary
convincing evidence for recessive pedigree with 31 affected persons in 18 congenital (infantile) glaucoma (PCG;
inheritance of juvenile glaucoma. siblings was reported from Slovakia by gene symbol, GLC3) is a specific,
Bonaiti et al21 concluded that about Gencikova and Gencik 26. inherited developmental defect in the
30% of congenital glaucoma cases trabecular meshwork and anterior
in the series they analyzed were Genetic defects chamber angle, which manifests in the
of an autosomal recessive type. In neonatal or infantile period and is more
Czechoslovakia, Gencik et al22 studied According to the Human Genome severe and difficult to manage than
45 gypsy families with 118 persons Organization (HUGO) Nomenclature other types.
with congenital glaucoma. Inheritance Committee,27 loci for congenital
was autosomal recessive with complete glaucoma are designated by GLC3, and There has been some debate as to the
penetrance. In addition, they studied letters are added to distinguish specific exact nature of the structural changes
81 non-gypsy families with 87 affected loci in order of their discovery. Till in the angle that are associated with
persons. Among these, 26.6% were date, 3 genetic loci have been linked the disease. The early postulation of an
only unilaterally affected and onset to PCG7: GLC3A at chromosome locus imperforate mesodermal membrane
was usually later and course milder. 2p21; GLC3B at chromosome locus covering the outflow channels has not
The population frequency was much 1p36; and GLC3C at chromosome locus been verified by electron microscopy.
lower and an excess of males (1.55:1) 14q24.3. Of these, only the GLC3A Several histopathological studies
was noted. The authors concluded that locus has been linked to a specific gene. have observed that the iris insertion
multifactorial inheritance is likely in This gene is called CYP1B1, and is the and anterior ciliary body overlaps the
the latter group. Ferak et al23 published largest known enzyme of the human posterior portion of the trabecular
observations on the high frequency cytochrome p450 pathway. meshwork.40. It was concluded that
during anterior chamber development,
the iris and ciliary body failed to recede
posteriorly. Tawara and Inomata41
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Subspeciality-Glaucoma
studied trabeculectomy specimens Fig 3. PCG presenting Fig 4. PCG presenting with Fig 5. PCG presenting with
from eyes of patients with PCG and with watering and scarred corneas large eyes and hazy corneas
observed that the juxtacanalicular area photophobia
was markedly thickened and consisted
of many layers of spindle-shaped cells Management Examination under anesthesia is the first
with surrounding extracellular matrix. The management of congenital step to gauge the severity of the disease
In general, structural studies agree that glaucoma starts with parental and extent of glauocmatous damage
that the developmental defect affects all counselling which should include a that thas occurred. The parameters to
areas of the trabecular meshwork. discussion of what is glaucoma; the be evaluated include corneal edema,
These developmental anomalies of need for surgery and possibilites of IOP, Cup-Disc ratio Panicker et al41
the anterior chamber angle prevent multiple surgeries, the need for life- have graded the severity of glauocama
drainage of aqueous humor, thereby long follow up and the combinaiton of depending upon the clinical features as
elevating intraocular pressure (IOP). problems to be tackled (IOP, Amblyopia given below in Table 1.
During the first 3 years of life, the management, Refractive correction,
collagen fibers of the eye are softer and Possible keratoplasty).
more elastic than in older individuals.
Thus, elevation of intraocular pressure Table 1. Severity index for grading PCG phenotypes
(IOP) in children younger than 3 years
of age (infantile glaucoma) causes rapid Clinical parameters Normal Mild Mod Severe/V severe
enlargement of the globe. The globe used for grading
enlargement occurs primarily at the
corneoscleral junction. As the cornea Corneal diameter Up to 10.5 >10.5-12 >12-13 >13
and limbus enlarge, the endothelium of
the cornea and Descemet’s membrane IOP Up to 16 >16-20 >20-30 >30
are stretched. This stretching can result C/D ratio 0.3-0.4 >.4-.6 >.6-.8 >.8
in a linear rupture of the Descemet’s Last recorded Va 20/20 <20/200:<20/400-
membrane (Haab’s striae). The Mild Severe NPL
Descemet’s membrane rupture may Corneal clarity No edema edema edema Sev edema + Haab’s
occur acutely, causing an influx of striae
aqueous into the stroma and epithelium,
resulting in sudden corneal edema. The
corneal edema produces photophobia,
blepharospasm, and tearing.
Fig. 2. Haab’s striae Tonometry pressure of 20 mm Hg or more should
Clinical features of PCG typically General anesthetics usually lower the be considered abnormal. Elevated
include tearing, photophobia, clouding IOP except for ketamine, which may IOP alone is not sufficient to confirm
of the cornea and buphthalmos increase IOP. IOP be checked in early a diagnosis of congenital glaucoma.
(enlargement of the globe) (Fig 3-5). The stage of anesthesia to reduce errors. Other signs of this disease (e.g., corneal
more serious consequence of elevated The Schiötz tonometer should be haze, increased corneal diameter, and
pressure is that it can rapidly lead avoided because it is not as accurate increased optic disc cupping) are as
to axonal loss and permanent visual as the Perkins hand-held applanation important as elevated IOP.
impairment in untreated children. tonometer. However it is better than
nothing! The Tono-Pen is convenient Corneal Diameter
and easy to use. Accurate measurement of corneal
size is important in the diagnosis and
The normal IOP in infants under follow-up examination of children
anesthesia is usually in the low teens. A with glaucoma. Using calipers for
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Subspeciality-Glaucoma
this purpose, the corneal diameter in its initial stages may not represent trabeculectomy combined surgery has
measurement should be taken from neuronal loss. Thus, posterior bowing been found to result in more favourable
limbus to a similar point 180° away at of the lamina cribrosa is a late outcomes and many surgeons prefer
the opposite limbus. The 95% ranges occurrence in adult glaucoma but it that approach (Fig. 6) The surgical
of normal corneal diameters are: 9.4 occurs early in infants. Glaucomatous success has been reported to be
mm to 11.0 mm at age 1 month, 10.5 cupping in infants, unlike in adults, is varied. In cases of refractory cases not
mm to 11.7 mm at age 6 months, and usually reversible after normalization responding to surgery, a repeat surgery
10.8 mm to 12.0 mm at age 12 months.42 of IOP. This was first reported in 1965 by is needed. Shunts in the form of valved
In congenital glaucoma, the diameter Chandler and Grant.43 The younger the and non-valved implants have been
of cornea may enlarge to as much as child, the faster this reversibility. Such reported to be successful after failure
17 mm. Changes in corneal diameter a rapid change in optic disc cupping of conventional surgery.
less than 0.5 mm in the follow-up is probably related to mechanical
examination should be interpreted changes cited earlier. Improvement in SECONDARY CHILDHOOD
cautiously. the amount of cupping may be limited GLAUCOMA
by many factorsincluding the extent of
Gonioscopy nerve fiber loss. Congenital glaucoma is responsible
for between 4% and 18% of childhood
A 14-mm Koeppe lens provides a clear Treatment blindness.43,44 In studies done in India,
view of the angle of the eye, and a hand- the disease accounts for 4.2-7% of all
held microscope with a Barkan light or The treatment of PCG is surgical. childhood blindness.44,45 But other
any type of illuminator is necessary for Medical management has a role as a glaucomas besides primary glaucoma
gonioscopy during anesthesia. If the temporizing measure until the child can contribute to the glaucomas in children.
cornea is cloudy, removing the corneal be posted for general anaesthesia. The Most cases of pediatric glaucoma have
epithelium clears the view. During surgical options include goniotomy, no specific identifiable cause and are
gonioscopy, the site of iris insertion trabeculotomy, trabeculectomy with considered primary glaucoma. When
should be evaluated carefully. In antifibrotic agents. A trabeculotomy- glaucoma is caused by, or associated
congenital glaucoma, the iris usually
is inserted anterior to scleral spur, and
the angle recess is poorly formed.
Funduscopy Fig. 6 .Trabeculotomy with trabeculectomy being performed under general anesthesia.
Partial thickness scleral flap raised (top left) Schlemm’s canal dissected (top right), Schlemms
Dilated fundus examination and disc canal cannulated with Haarms’ trabeculotome (bottom left and right).
evaluation are essential in diagnosing
congenital glaucoma. Cupping of the
optic disc occurs much faster than in
adults. Optic disc cupping larger than
30% of disc diameter, especially if
asymmetric between two eyes, is strong
evidence that the disc is under pressure
and may be glaucomatous. Changes
in the optic disc occur readily with
changes in IOP in infants.28 Richardson
and Shaffer28 in 1966 and Khodadoust26
in 1968 documented the early response
of the infant disc to elevated IOP. When
congenital glaucoma is diagnosed
at birth, there us often a significant
degree of optic disc cupping. If IOP is
not controlled, increased cupping can
be demonstrated in 4 to 6 weeks. This
early rapid change in disc contour may
be related to mechanical distortion
in the disc supporting elements, and
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Subspeciality-Glaucoma
with a specific condition or disease, it Sturge-weber syndrome Axenfeld Reiger Syndrome
is called secondary glaucoma. These (encephalofacial Axenfeld’s anomaly (Figure 9)
disorders, are characterized by angiomatosis, is characterized by a prominent
improper development of the eye’s encephalotrigeminal anteriorly displaced Schwalbe’s line
aqueous outflow system and usually angiomatosis) termed posterior embryotoxon along
manifest in infancy and childhood. with bands of iris tissue across the
Early recognition of and appropriate Sturge-Webersyndromeischaracterized anterior chamber angle attached to
therapy for the child with secondary by a flat facial hemangioma which this thickened Schwalbe’s line. The
glaucoma can significantly improve a follows the distribution of the fifth disease is autosomal dominant and
child’s visual future. cranial nerve. Glaucoma is seen in usually is bilateral. Approximately 50%
nearly 50% of the patients and is is more of patients with Axenfeld’s anomaly
Aniridia (Figure 7) likely to appear in infancy than later. develop glaucoma. Riegers anomaly
When oculodermal melanocytosis is characterized by significant iris
Aniridia is a bilateral congenital and nevus flammeus (phakomatosis abnormalities, ranging from marked
anomaly in which there is profound pigmentovascularis) occur together, hypoplasia of the anterior iris stroma
hypoplasia of the iris in frequent with each extensively involving the to pupillary correctopia. The term
association with multiple ocular globe, there is a strong predisposition Rieger’s syndrome is applied when the
anomalies, such as peripheral corneal for congenital glaucoma. Sturge- ocular abnormalities are associated
pannus and keratopathy, foveal Weber glaucoma is present when with dental, facial, or other systemic
hypoplasia, diffuse retinal dysfunction the facial hemangioma involves the abnormalities. The glaucoma may occur
as seen on electroretinography, lids or conjunctiva. If the glaucoma in infancy and responds to goniotomy
impaired acuity with nystagmus, occurs in infancy, the mechanism is or trabeculotomy. Trabeculectomy
cataract and ectopia lentis, and optic an isolated trabeculodysgenesis type with antimetabolite, combined
nerve hypoplasia. In most cases of angle anomaly with or without trabeculectomy-with-trabeculotomy or
glaucoma does not develop until abnormalities in the canal of Schlemm glaucoma tube procedure are the other
later childhood or early adulthood. In and juxtacanalicular tissue. As the options.
infantile-onset cases, the glaucoma is child ages, the elevated IOP is due
thought to be due to a trabeculodysgenic to an elevation of episcleral venous Figure 9: Seven year old with Axenfeld
anomaly of the anterior chamber angle. pressure. Medical therapy involves oral Rieger Anomaly.
If aniridic glaucoma occurs in infancy, propranolol besides the antiglaucoma
a trabeculotomy is the procedure medications and definitive therapy is
of choice. Other options include usually surgery. Post-operative course
trabeculotomy alone, trabeculectomy is often complicated by hypotony
with or without antimetabolites. In and choroidal detachments46 due
cases of failed trabecular surgery, to rapid expansion of the choroidal
glaucoma implants or ciliodestructive hemangioma with effusion of fluid
procedures have been used, often with into the suprachoroidal and subretinal
more than two procedures per eye spaces. (figure 8)
required.
Spherophakia
Weill-Marchesani syndrome
includes short stature, brachydactyly,
microspherophakia, glaucoma, and
ectopia lentis. The lenses are frequently
small (microspherophakia; Figure 10),
with loose zonules; they are more likely
to dislocate than in cases of Marfan
syndrome and do so in a downward
Figure 8: Six year male; known case of direction. Glaucoma occurs due to
Figure 7: 4 year old child with aniridia. Sturge weber ; underwent glaucoma angle-closure and treatment includes
Note the rudimentary iris stump and clear drainage device and presented with complex lensectomy, IOL insertion, and
lens with intact zonules hypotony and choroidal detachment. glaucoma shunt surgery.
64 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Figure 10: Microspherophakia a locus (GLC3A) for primary congenital praesenilen und senilen Glaukoms.
glaucoma (Buphthalmos) to 2p21 and Genetica 1950;25: 79-125.
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Turacli ME, Aktan SG, Barsoum-Homsy Genet 1999; 36:290-4. cause of primary congenital glaucoma
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18. Bejjani BA, Stockton DW, Lewis RA, the GLC3A locus on chromosome 2p21.
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31. Friedman JS, Walter MA. Glaucoma 38. Reddy AB, Kaur K, Mandal AK, Ophthalmic Epidemiol. 2008 May-
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66 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Anterior Segment Optical
Coherence Tomography (ASOCT)
for Evaluation of Filtering Bleb
Mayuri Khamar M.S.
Glaucoma Consultant, Occura Eyecare & Research Center, Ahmedabad
Ex. Associate Professor, BJ Medical College, Ahmedabad
Like any other surgical process, Figure 1: Aqueous passage avoid exerting any pressure on the globe
trabeculectomy is also followed by or bleb while elevating lid particularly
healing process which is associated Figure 2: Sub scleral aqueous passage during early post- operative period.
with fibrosis. Pattern of fibrosis Filtering bleb scanning with Two good quality scans radial and
determines morphology of bleb AS-OCT tangential through the maximum point
and long term outcome. Slit lamp Patients is made to sit comfortably in of elevation on the bleb are taken. It is
evaluation of bleb following surgery front of the machine by adjusting height advisable to have minimum three scans
helps in understanding of changes in of machine and chin rest. Patient need prior to selecting the better one.
bleb morphology over time. However to look down, and if required upper lid
its resolution/precision is relatively low is elevated gently to expose the upper
for assessing changes in bleb wall as well extent of the bleb. It is important to
as within the bleb. Anterior segment
Optical coherence tomography (AS -
OCT) has better resolution and precision
and bridges this gap. AS - OCT provides
high-resolution images, with an axial
resolution ranging from 3 to 20 µm. It
helps in generating information about
height, width and length of the bleb;
bleb wall reflectivity and thickness, bleb
cavity and its contents like cystic spaces,
trabeculectomy window, aqueous
passage from anterior chamber to bleb,
etc. (Figure 1, 2). Evaluation of changes
over time is helpful in understanding
the fibrotic process. Serial evaluation is
helpful in prognostication, appropriate
counselling and timely intervention.
It is also helpful in research related
to pathogenesis of subconjuctival
fibrosis, evaluation of various surgical
procedure as well as interventions to
improve outcome.
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Subspeciality-Glaucoma
Evaluation of bleb scan
AS-OCT provides quantitative as well as qualitative
parameters about bleb.
Quantitative parameters Figure 7: Microcyst
Bleb: Quantitative bleb parameters include height, length and
width of bleb, wall thickness and cyst size.
Trabeculectomy window: It is possible to evaluate size of the
trabeculectomy window and generate information about
changes over time.
Qualitative parameters
Bleb wall reflectivity –which is further classified as uniform
(figure 3) or multiform (figure 4,5)
Figure 3: Uniform bleb reflectivity Figure 8: Bleb following mitomycin –C
Figure 4: Multiform bleb reflectivity Hyper reflective areas / bleb wall thickness
Visible route beneath the scleral flap. (figure 1,2)
Figure 5 : Multiform wall reflectivity blebs:
Bleb wall pattern– which is to be further classified as having Prognostic value: Ability to study bleb changes over time
conjunctival/subconjuctival separation (figure 6) micro-cysts with high resolution and precision has led to assigning
(figure 7), and multiple internal pattern layers (figure 8). prognostic value to some of the bleb parameters .
Trabeculectomy Window : The width of filtration openings
at 0.5 months is indicative of speed of subconjuctival fibrotic
process and has a good prognostic value with wider opening
associated with long term functioning of bleb and narrow one
with early failure.
Bleb reflectivity: In the bleb walls having a uniform reflectivity
in early postoperative period as early as 1 month suggest a
poor bleb function, and predict early bleb failure. (Figure 3)
Presence of areas of hyporeflectivity (multiform walls) in the
early postoperative period suggests long term functioning
of bleb (figure 4, 5). Hyporeflectivity in mature bleb walls
whether in a cystic or layered pattern, represent the collections
of aqueous humor and is associated with functioning bleb.
Subconjunctival separation (or Subconjunctival fluid spaces):
Subconjuctival separation also predicts good functional bleb
(Figure 6).
Microcysts: Presence of microcysts in blebs in the early or late
postoperative period are associated with good function of the
mature bleb (figure 7). Loss / absence of microcyst is indicative
of bleb fibrosis.
Figure 6: Conjunctival separation with multiple internal layers Diagnostic value:
Bleb Structure: Information about bleb structure helps
in identifying reasons for failure eg. Early closure of inner
osteum by iris, fibrosis around scleral flap with open inner
ostium, encapsulated bleb with intact aqueous channel
created surgically. This helps in appropriate intervention.
68 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Onset and progression of conjunctival separation. of trabeculectomy with Mitomycin C. J
subconjuctival fibrosis: Rapid ii. Express shunt : AS-OCT is Glaucoma. 2003;12:430-435.
progression in early postoperative
period may suggest use of anti-fibrotic helpful in determining internal 4. Yamamoto T, Sakuma T, Kitazawa Y.
agents like 5-FU. drainage and changes with time. An ultrasound biomicroscopic study
e. Valve/Stent procedures : AS-OCT of filtering blebs after Mitomycin
Research helps in demonstrating tube C trabeculectomy. Ophthalmology.
Relationship with intervention : position as well as bleb around it. 1995;102:1770-–1776.
a. Simple trabeculectomy
b. Trabeculectomy with mitomycin-c Conclusion 5. Savini G, Zanini M, Barboni P. Filtering
AS-OCT identifies the internal structures blebs imaging by optical coherence
: (Figure 8) of the bleb, thereby providing better tomography. Clin Experiment
Mitomycin use during understanding of the bleb morphology. Ophthalmol. 2005;33:483-–489.
AS OCT (non contact) can be a good
trabeculectomy is associated with adjunct to clinical classification in 6. Babighian S, Rapizzi E, Galan A.
large cystic pattern (hyporeflective assessing functional outcome of bleb Stratus OCT of filtering bleb after
cystic spaces) or multiple predicting its success or failure, at early trabeculectomy. Acta Ophthalmol
internal layers and/or areas of post-operative period. Provides scope of Scand. 2006;84:270-–271.
subconjunctival separation in early early intervention in blebs with poor
postoperative period . Over a time functional outcome (Steroid, 5-FU, 7. Singh M, Chew PT, Friedman DS, Nolan
they get obliterated due to fibrosis Needling, Release/ suturolysis etc.) WP, See JL, Smith SD, et alet al. Imaging
and are restricted mainly to the of trabeculectomy blebs using anterior
deeper layers of the bleb wall at 6 Bibilography segment optical coher nce tomography.
months post-operatively. Ophthalmology. 2007;114:47-53.
c. Trabeculectomy with releasable 1. Picht G, Grehn F. Classification of
suture: filtering blebs in trabeculectomy: 8. Guthoff R, Klink T, Schlunck G,
Suturolysis or releasing of suture Biomicroscopy and functionality. Curr Grehn F. In vivo confocal microscopy
associated with changes in bleb Opin Ophthalmol. 1998;9:2-–8. of failing and functioning filtering
wall hyporeflectivity. blebs: Results and clinical correlations. J
d. Internal drainage devices : 2. Cantor LB, Mantravadi A, WuDunn D, Glaucoma. 2006;15:552-–558.
i. Ologen implant : Ologen is Swamynathan K, Cortes A. Morphologic
classification of filtering blebs after 9. Nakano N, Hangai M, Nakanishi H,
a biodegradable implant. glaucoma filteration surgery: The Inoue R, Unoki N, Hirose F, et alet
Following surgery it gets Indiana bleb appearance grading scale. J al. Early trabeculectomy bleb walls on
degraded overtime. (figure Glaucoma. 2003;12;266-271. anterior-segment optical coherence
9a, b, c, d). This is associated tomography. Graefes Arch Clin Exp
with micro cyst formation, 3. Sacu S, Rainer G, Findl O, Ophthalmol. 2010;248:1173
Georgopoulos M, Vass C. Correlation
between the early morphological
appearance of filering blebs and outcome
Corresponding Author:
Figure 9: Ologen bleb
Absorption of biodegradable collagen implant creates aqueous pockets below it with
microcystic areas away from it. Complete absorption of Ologen is associated with shrinkage
of bleb.
9 A : Post operative day 1 9 C : Post operative six month Dr Mayuri Khamar M.S
9 B : Post operative day 8 9 D : Post operative 12 months Glaucoma Consultant, Occura Eyecare &
Research Center, Ahmedabad
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Subspeciality-Glaucoma
Bleb Needling: Effective Safe
Procedure to Revive Failing Bleb
Kirti Singh1, Arshi Singh2
1. Glaucoma Division, Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi
2. Baba Saheb Ambedkar Medical College & Hospital, New Delhi
Trabeculectomy success requires by lysing episcleral and subconjunctival improved the success rate.9.10 Shin et
minimal wound healing response fibrosis. al and Mardelli et al further refined
resulting in subconjunctival/ subscleral Bleb needling in its nascent form was it by use of intraoperative 5-FU and
fibrosis, which till date remains the first done by Ferrer in 1941 by incising mitomycin C (MMC) respectively.11,12
most common cause of bleb failure. 1,2,3 subconjunctival scar tissue with a Success rates of these initial studies
Subconjunctival fibrosis, the nemesis spatula.7 The success behind this were high ranging from 80- 92%.
of successful trabeculectomy has racial procedure and pathophysiology of bleb
propensity, occurring more frequently failure was explained by Swan KC to be Indications of bleb needling:
and more rapidly in pigmented races episcleral cicatrization.8 The procedure yy Failing blebs with high intraocular
of Asian and Afro Caribbean ethnicity4 gained acceptance and antifibrotic
Anti-metabolites like 5 Fluorouracil adjuncts initiated by Ewing and pressure
and Mitomycin C inhibit this fibrosis by Stamper in the form of postoperative yy Encapsulated bleb/ Tenon cyst
inhibiting fibroblasts in the area treated 5-fluorouracil (5-FU) injections further yy Walling off of bleb with normal
by them. Although this antifibrotic
augmentation enhances bleb survival pressures
by 80-95%, the success is short lived and
effect wanes off to 50- 60% efficacy over Fig 1. Impending failure of bleb. a Corkscrewing of vessels b. persistent, angry vascularization
a period of 5 years.5,6 c. Persistent angry vessels with flattening of bleb d. Localization of bleb with reduction in
height
Bleb failure due to subconjunctival,
subscleral fibrosis is an event with
high probability in the life of a filtering
bleb. In this situation the standard
option is to initiate stepped up anti-
glaucoma medications to keep the
intraocular pressure in the target
range. However use of anti-glaucoma
medications with their side effects,
recurring cost, compliance issues and
requirement for monitoring make this
option unattractive. A procedure which
could undo the fibrosis blocking the
filter and re-establish aqueous flow
would be a very welcome alternative.
Bleb needling was envisaged as this
alternative and multiple reports over
last four decades have proven its worth.
A simple, relatively non-invasive,
effective, safe procedure to revive a
failing trabeculectomy bleb it works by
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Subspeciality-Glaucoma
Case selection is based on careful Fig 2. Gonioscopy shows the iris tissue scarred interface adjacent to bleb by
examination of bleb morphology. blocking internal sclerostomy to and fro (Jack-hammer) movements
The signs heralding bleb failure being and by sideway sweeping motions
persistent, angry vascularization, After informed consent the procedure to puncture bleb wall, increase it’s
corkscrewing of vessels, reduction is performed under topical anesthesia permeability and restore aqueous
in bleb height, loss of conjunctival under microscope in operation theatre drainage. The entry point acts as a
microcysts, and reduction of or with slit lamp in outpatient sitting, fulcrum from where needle launches
conjunctival mobility over bleb. Fig with the former being preferred. The itself into multiple directions. Fig 3 The
1 Such bleb morphology may or may OR offers the advantage of a more needle tract should be kept bevel up and
not be associated with increase in controlled setting and may allow for be clearly visible at all times. Careful
intraocular pressure in the initial phase. more extensive treatment. attention is given to avoid inadvertent
Anterior segment ocular coherence buttonholing of overlying conjunctiva.
tomography (ASOCT) aids in diagnosis Under aseptic conditions eye is draped A needle bent around 45-60º redirects
by picking up early failure reduction of and by using a 26, 27 or 30 -gauge needle force, avoids jerky movements and
microcystic spaces. on a 1 ml tuberculin syringe. A 26-gauge facilitates entry. At intervals the
needle is preferred due to its sturdiness subconjunctival space is ballooned by
Poor response to needling is seen in high and resistance to bending during injecting the 5 FU/MMC solution and
IOP > 30 mm Hg, lack of antifibrotic use disruption of scar tissue then the lysis continued. A gritty feel
during initial trabeculectomy, and poor and its break ca be felt as the fibrotic
response manifest by non -lowering Subconjunctival space is entered 3-4 bands are cut. At the end the needle is
of IOP to less than 10 mm Hg in the mm away from edge of bleb in a self- withdrawn from the entry point, which
immediate post needling period.13, 14 sealing Z-tract. The syringe contains 0.5 is then sealed by holding a cotton swab
ml of freshly prepared 5-Fluorouracil in situ for a minute, sealing the site with
Bleb maturity plays a role with early 10 mg/mL dilution or 0.1 mL of 50 a blob of viscoelastic solution or wet
intervention in immature blebs, mg/mL the former being preferred. field cautery. Often two entry points
before frank fibrosis sets in improves Alternatively freshly prepared 0.1 ml of are required to approach the scarred
success, although reported benefits Mitomycin C of 0.2mg/mL or 0.4 mg/ ml bleb from both sides (temporally and
have been reported till 30 years dilution is used.12 nasally).
post trabeculectomy15 Most authors
advocate early needling before fibrosis Patient is instructed to look down Modification
is deeply entrenched, preferably within and magnification is kept minimum a. A modification of this procedure is
4 months of surgery, with others to obtain best possible exposure of
advocating waiting for longer interval entire bleb. Subconjunctival fibrosis to inject the antifibrotic drug - 0.5
to achieve better outcomes. 11, 16 is disrupted by multiple holes in the ml of 5-FU (10 mg/mL) or 0.1mL of
MMC of (0.2or 0.4 mg /mL dilution)
Adjuvant use of total of 0.04 mg of MMC), as a single
subconjunctival injection 5 to 10
antimetabolites mm from bleb area. The fluid is
then milked with a rolling motion
Antimetabolite use inhibits fibroblast using a cotton swab by applying
proliferation and freezes scarring pressure in a rolling motion over the
process in the compromised tissue of conjunctiva next to the injection
failing bleb and maintains long-term
filtration in bleb needle revisions.
Antimetabolites 5 Fluorouracil and
Mitomycin C have been extensively
used as an adjunct.10, 11, 12 Success rates
after the procedure vary from 60- 72 %,
over a 1 to 2 year period follow up. 1, 17, 18
Procedure: Fig 3. Needling sequence a. Entry of needle b Injection of fluid with MMC/ 5FU c. Needling
Pre-operative gonioscopy is mandatory done, note small subconjunctival bleed (denoting cut fibro-vascular band) d. Temporal side
to rule out blockage of inner sclerostomy needle withdrawn, entry point sealed and needle re-introduced from nasal side
by iris tissue, ciliary tissue or vitreous, as
that would entail a different procedure.
Fig 2
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Subspeciality-Glaucoma
site. The needling is commenced anterior chamber is reformed with Success is heralded by alteration in bleb
after 15-20 minutes after injecting BSS after removing the viscoelastic appearance with increase in size, height
the MMC. solution. The paracentesis site is and/ or reduction of vascularization,
then hydrated and section checked improvement in conjunctival motility
b. Further lifting up of visible for water tightness. External bleb accompanied by control of IOP, over
superficial scleral flap with the needling is then performed with a period of 3-7 days. Restoration of
needle until the give is felt due 5 FU or MMC, using a 26G needle aqueous flow is indicated by flat blebs
to entry into anterior chamber, is inserted 3 mm away from the becoming elevated, encapsulated blebs
attempted if bleb flattening does not demarcated bleb. becoming flat and diffuse along with
respond to episcleral needling. This reduction in IOP. Fig 5
is then followed by a controlled, d. Other antifibrotic options used
gentle lysis of subscleral fibrosis have been Triamcinolone-aceton- Patients are instructed to use topical
using the same needle.12, 19 ide and bevacizumab (Avastin, Ge- steroid-antibiotic 4 times daily for 1
nentech)20, 21 week tapered over 2-3 weeks.
c. Internal bleb revision combined:
Devised by the author, this e. Transconjunctival administration, Success & Repeatability
procedure is done in cases where not subconjunctival injection of
internal ostium is plugged by iris MMC.22 An immediate reduction in IOP
tissue and is performed under portends success. Longer duration of
peribulbar anaesthesia in operating f. Intraoperative optical coherence scarring, larger area of scarring, higher
theatre. After cleaning and draping tomography (iOCT) guided bleb pre-needling IOP and increased number
the eye, the surgeon positions her/ needling to confirm this lysis. 23, 24 of needlings predispose to failure.17The
himself temporally and creates a success rates are similar in for both
clear corneal paracentesis with a Post-operative regimen open angle and closed angle glaucoma
MVR blade, within 3 clock hours with a recent study reporting 58% and
of the blocked sclerostomy site, After ensuring that no bleb leakage is 63% success respectively.17
in temporal quadrant. Dispersive occurring, the conjunctiva is rinsed
viscoelastic is injected into with sterile saline and antibiotic steroid The procedure can be repeated after
anterior chamber through the injection given at a site 180 degrees an interval of 2-3 months. In cases
paracentesis and a vitreous sweep, away from the bleb. The eye is patched of successive failure of 2 needling
straight rod manipulator is used for few hours on removal of which interventions, the surgeon should plan
to release the incarcerated iris antibiotic steroid combination is given surgical revision of trabeculectomy.
tissue from internal ostium. Fig 4- 6 times a day for 2-3 weeks depending
4 The straight rod instrument is on clinical response of bleb morphology
subsequently swept through the and IOP.
internal sclerostomy opening
into the dissected plane beneath
superficial scleral flap to release
the subscleral fibrosis. Once the
peripheral iridectomy becomes
visible, the rod is withdrawn and
Fig 4. Ab interno Internal revision, Fig 5 a, b. Depict the failing bleb revived, with reduction in angry vasculature and increase
unplugging internal sclerostmy from in extend and height of bleb c, d Depict improvement in microcystic spaces on anterior
incarcerated iris tissue . segment OCT
72 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Complications 8. Swan KC. Reopening of nonfunctional 20. Tham CC, Li FC, Leung DY, Kwong
Complications reported with needling filters—simplified surgical techniques. YY, Yick DW, Chi CC, Lam DS. Intrableb
revision are infrequent and minor.18 Trans Am Acad Ophthalmol triamcinolone acetonide injection
They include subconjunctival Otolaryngol. 1975; 70: 342-348. after bleb-forming filtration surgery
hemorrhage, conjunctival buttonhole, trabeculectomy, phacotrabeculectomy,
hyphema. Rarely corneal toxicity due 9. Pederson JE, Smith SG. Surgical and trabeculectomy revision by
to leakage of 5 FU has been reported. management of encapsulated filtering needling): a pilot study. Eye (London).
Infrequently inadvertent perforation blebs. Ophthalmology. 1985; 92:955- 2006; 20 (12):1484-6.
can cause bleb leak, shallow anterior 958.
chamber, hypotony, choroidal effusion 21. Kahook MY, Schuman JS, Noecker
and suprachoroidal bleed.25 10. Ewing RH, Stamper RL. Needle RJ. Needle bleb revision of
revision with and without 5-FU for the encapsulated filtering bleb with
Conclusion treatment of failed filtering blebs. Am J bevacizumab. Ophthalmic Surg Lasers
Bleb needle revision aims to re-establish Ophthalmol. 1990; 110: 254-259 Imaging. 2006; 37:148-150
the fistula by improving vascular
permeability of bleb walls. This 11. Shin DH, Juzych MS, Khatana AK, 22, Iwach AG, Delgado MF, Novack GD,
effective, simple, safe, cost economical, Swendris RP, Parrow KA. Needling et al. Transconjunctival mitomycin-C
conjunctival sparing procedure should revision of failed filtering blebs with in needle revisions of failing filtering
be attempted in every failed or failing adjunctive 5-fluorouracil. Ophthalmic blebs. Ophthalmology. 2003; 110: 734-
bleb at any stage of bleb maturity before Surg. 1993; 24:242-248 742
subjecting the patient for a repeat
trabeculectomy. 12. Mardelli PG, Lederer CM Jr, Murray PL, 23. Dada T, Angmo D, Midha N, Sidhu
Pastor SA, Hassanein KM. Slit-lamp T. Intraoperative Optical Coherence
References needle revision of failed filtering blebs Tomography Guided Bleb Needling. J
using mitomycin C. Ophthalmology. Ophthalmic Vis Res. 2016; 11 (4):452-4.
1. Liu W, Wang J, Zhang M, Tia Y and 1996; 103: 1946-1955.
Sun Y. Comparison of subconjunctival 24. Dada T, Vengayil S, Gadia R, Gupta
Mitomycin C and 5 -Fluorouracil 13. Shin DH, Kim YY, Ginde SY, Kim PH, V, Sihota R. Slit lamp-optical coherence
injection for needle revision of Eliassi-Rad B, Khatana AK, Keole NS. tomography-guided needling of failing
early failed trabeculectomy blebs. J Risk factors for failure of 5-fluorouracil filtering blebs. Arch Ophthalmol. 2008;
Ophthalmol 2016:3762674 needling revision for failed conjunctival 126 (2):284-6.
filtration blebs. Am J Ophthalmol. 2001;
2. Azuara Blanco A, Katz LJ. Dysfunctional 132:875-880 25. N. Palejwala, P. Ichhpujani, G. Fakhraie,
filtering blebs. Survey Ophthalmology J. S. Myers, M. R. Moster, and L. J. Katz.
1998:43(2): 93-126 14. Broadway DC, Bloom PA, Bunce C, Single needle revision of failing filtration
Thiagarajan M, Khaw PT. Needle revision blebs: a retrospective comparative
3. Palmberg P. The failing filtering bleb. of failing and failed trabeculectomy case series with 5- fluorouracil and
Ophthalmology Clinics of North blebs with adjunctive 5-fluorouracil: mitomycin C. European Journal of
America. 200; 13(3): 517-530 survival analysis. Ophthalmology. 2004; Ophthalmology. 2010; 20 (6):1026–34.
111:665-673.
4. Husain R, Clarke JC, Seah SK, Khaw Corresponding Author:
PT. A review of trabeculectomy in East 15. Ung CT, Von Lany H, Claridge KG. Late
Asian people-the influence of race. Eye bleb needling 2003; 87(11):1430-1. Dr. Kirti Singh, MD, DNB, FRCS, FAIMER
(Lond). 2005; 19 (3):243-52. Dir Professor of Ophthalmology,
16. Gutierrez-Ortiz C, Cabarga C, Teus MA. Guru Nanak Eye Center and
5. Wong TT, Khaw PT, Aung T, Foster PJ, Prospective evaluation of preoperative Maulana Azad Medical College,
Htoon HM, Oen FT, et al. The Singapore factors associated with successful Ranjit Singh Marg, New Delhi 110002
5‑fluorouracil trabeculectomy study: mitomycin C needling of failed filtration
Effects on intraocular pressure control blebs. J Glaucoma. 2006; 15:98-102.
and disease progression at 3 years.
Ophthalmology 2009; 116:175‑84. 17. Tsai AS, Boey PY, Htoon HM, Wong
TT. Bleb needling outcomes for failed
6. Five‑year follow‑up of the fluorouracil trabeculectomy blebs in Asian eyes: a
filtering surgery study. The Fluorouracil 2-year follow up. Int J Ophthalmol. 2015;
Filtering Surgery Study Group. Am J 8(4):748-53.
Ophthalmol 1996; 121: 349‑66
18. Ray VP, Choudhari N. Rescue of failing
7. Ferrer H. Conjunctival dialysis in the or failed trabeculectomy blebs with
treatment of glaucoma recurrent after slit-lamp needling and adjunctive
sclerectomy. Am J Ophthalmol. 1941; 24: Mitomycin C in Indian eyes, Indian J
788-790. Ophthalmol 2018, 66 (1): 71-76
19. Greenfield DS, Miller MP, Suner IJ,
Palmberg PF. Needle elevation of the
scleral flap for failing filtration blebs
after trabeculectomy with mitomycin C.
Am J Ophthalmol. 1996; 122:195-204
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Subspeciality-Glaucoma
Use of Artificial Intelligence in
Glaucoma
Suruchi Bhalla1, Kanika Jain2, Ashwini Kulkarni3
1. Masters in Data Science, Macquarie University, NSW, Australia
2,3. Department of Ophthalmology, DDU Hospital, New Delhi
Abstract: Glaucoma is irreversible and progressive loss of vision due to damage to the retinal ganglion cells. While an early
intervention could minimise the risk of vision loss in glaucoma, its asymptomatic nature makes it difficult to diagnose until a
later stage. The diagnosis of glaucoma is a multimodality approach that is heavily dependent on the experience and expertise
of a clinician. The application of artificial intelligence (AI) algorithms in ophthalmology has improved our understanding of
much retinal, macular, choroidal and corneal pathology. Over the years, several AI techniques have been proposed to help
detect glaucoma by analysis of functional and/or structural ocular images. Moreover, the use of AI has also been explored to
improve the reliability of ascribing disease prognosis. This review summarises the role of AI in the diagnosis and prognosis of
glaucoma, discusses the advantages and challenges of using AI systems in clinics and predicts likely areas of future progress.
Introduction of ophthalmology, a number of AI tasks normally requiring human
approaches have been explored for intelligence, such as visual perception,
Glaucoma is an incurable condition the diagnosis of retinal,12 choroidal,13 speech recognition, decision-
that requires lifelong treatment macular,14,15 and corneal pathologies.16,17 making, and translation between
and monitoring, and is the second Modern AI algorithms are especially languages.”18 Artificial Intelligence
largest cause of irreversible blindness tailored to extract meaningful features is the science of applying computer
worldwide.1 The central event in from complex and high-dimensional algorithms to replicate intelligent
glaucoma is the irreversible damage data. Consequently, a number of human-like behavior.
of retinal ganglion cell (RGC) axons AI studies have been proposed for
which undergo programmed cell the diagnosis and management of Machine Learning (Figure 1)
death (apoptosis) resulting in vision glaucoma based on the interpretation Defined as “the capacity of a computer
loss.2 While an early diagnosis could of functional and/or structural ocular to learn from experience, i.e. to modify
minimise the risk of permanent vision information. There are multiple goals its processing on the basis of newly
loss, nearly half the patients affected by of artificial intelligence in glaucoma. acquired information.”19 In Machine
glaucoma remain undiagnosed until The first aim has been detection of Learning, the algorithms learn on their
a relatively late stage due to the slow glaucoma by classifying visual fields, own by trial and error, without being
and asymptomatic nature of the disease optic nerve imaging, or other clinical explicitly programmed the steps to do
in its earlier stages.3 Once diagnosed, data. Second, artificial intelligence has a task.
predicting the progression of glaucoma been utilized to detect worsening earlier
is a complex endeavour that is time than conventional algorithms. Finally, Neural Network
consuming, subjective and heavily machine learning has been applied to The software is built as a network of
dependent on the clinician’s experience studying risk factors for glaucoma, and neurons communicating with each
and expertise, and requires multiple quality of life. This review summarises other with multiple inputs modifying
clinical tests.4,5 This means that cases the role of AI in glaucoma, the clinical the output, and often have a feedback
of overtreatment and undertreatment advantages and challenges, and projects loop for learning.
are presently inevitable.6 Timely and potential future applications of AI in
reliable structural and functional glaucoma. Deep Learning
evaluation of the eye could help in the Deep learning is a class of machine
early diagnosis of glaucoma, and to Understanding AI Algorithms learning algorithms that uses multiple
better predict its progression.7,8 In recent layers to progressively extract higher
years, artificial intelligence (AI)-based Artificial Intelligence level features from the raw input. For
systems have started to revolutionise example, in image processing, lower
the healthcare industry.9-11 In the field Defined as “theory and development layers may identify edges, while higher
of computer systems able to perform
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Subspeciality-Glaucoma
Fig. 1 AI Algorithms fully labelled data set toward correct handling low-dimensionality numeric
outputs through human involvement, data (eg, simple numbers such as the
layers may identify the concepts usually by being provided a diagnosis vertical cup-to-disc ratio, intraocular
relevant to a human such as digits or for each training input. In unsupervised pressure (IOP), age and sex.
letters or faces.20 It is an advanced level learning, the algorithm (eg, GMM, ICA) The second category includes the
of neural networks. is trained with an unlabelled data set sophisticated variants of the ANNs
(eg, only clinical parameters as inputs) known as convolutional neural
The AI algorithms discussed in this in an attempt to identify new patterns/ networks (CNN) (Figure 2). They
review can be broadly classified into trends. Unsupervised algorithms are are well suited for exploiting high
two categories based on the complexity able to take raw data and separate it dimensionality data (eg, fundus
of the data they handle. into classes which may or may not and OCT images) through multiple
match existing clinical knowledge and interconnected levels of data
The first category consists of machine therefore may demonstrate something abstraction. Convolution layers (layers
learning classifiers (MLC) and artificial previously unknown to experts. Such of filters) attempt to organically extract
neural networks (ANN). MLCs such as algorithms are typically well suited for the features (eg, information on texture,
random forest (RF), logistic regression edges, intensity, thickness) that best
(LR), support vector machine (SVM), represent the task (eg, identifying the
Gaussian mixture model (GMM) and presence of a pathology, identifying
independent component analysis a specific tissue) of the algorithm.
(ICA) are clustering algorithms that Through an iterative learning process
are extensions of classical statistical that aims to minimise the error between
modelling. ANNs, on the other hand, the output of the network (eg, predicted
are biologically inspired algorithms diagnosis) and the ground truth (eg,
that pass the input data through a series clinical diagnosis), weights (parameters)
of interconnected nodes (artificial of the extracted feature maps (to decide
neurons), and continuously modify the influence of each feature towards
the weights of each node to obtain the the final decision) are continuously
desired classification. Machine learning refined until the optimal weights (least
classifiers (MLCs) are algorithms that error between the network output and
process inputs and provide a specific the ground truth) are identified.
output that serves to classify or grade In the recent years, Deep Learning (DL),
the input. These algorithms learn to an advanced and powerful incarnation
take input data (eg, clinical parameters)
and automatically make a prediction Fig. 2 Artificial Neural Network Architecture
(eg, presence of pathology, glaucoma
severity) through a supervised or
unsupervised learning process. In
supervised learning, the algorithm (eg,
SVM, RF, ANNs, LR) is trained with a
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Subspeciality-Glaucoma
of the CNNs, has become the go-to AI approach of choice in DL. For instance, AI for evaluation of
approach in the field of medical imaging jointly understanding the textural
for segmentation, enhancement and information (eg, hyper-reflectivity) Intraocular Pressure (IOP)
diagnostic applications.21 It allows and spatial arrangement (eg, between
for more complex inputs (e.g, entire the retinal layers and choroid) might Prediction of IOP trends from previous
images), and for several intermediate be crucial for identifying the retinal data and medications would be a useful
layers thus allowing to make more pigment epithelium layer while and plausible use of AI. As of now, AI
sophisticated decisions; however, the learning to segment the ONH tissues was used for evaluation of data from
tradeoff is that it requires very large data from OCT images. Nevertheless, a Sensimed Triggerfish (Sensimed AG,
sets to train more complex networks. hybrid of traditional and advanced Lausanne, Switzerland). Martin et al
‘Automated feature engineering’ (ie, AI algorithms is also being explored used data from 24 prospective studies
automatically identifying the best set to increase the robustness of these of Triggerfish using Random Forest
of features in the data that influence the predictive models. (Fig 3) Modelling (a machine learning method)
performance of the algorithm) is the to identify the parameters associated
with glaucoma patients.22
Figure 3: Convolutional neural network framework. (a) One or more filter functions reduce
portions of the image (green box) into mathematical representations, creating a feature map AI for evaluation of functional
(gray circle). (b) Pooling functions combine similar statistics from extracted features. (c)
Fully connected layers are used in the classification process, in which each node is connected damage In Glaucoma
with every other node in the preceding layer. Multiple repetitions in multiple layers yield a
final output. In the earliest study reported in 1994,
Goldbaum et al23,24 proposed the use
of ANNs to interpret visual fields
(VF) data from standard automated
perimetry evaluations. When trained
on the absolute threshold sensitivity
(age and VF values read in sequence
from nasal to temporal), the ANN
was able to detect glaucomatous eyes
almost as proficiently as a trained
reader (ANN and expert agreement:
74%). Subsequently, other studies25-
27also concluded that ANNs and
MLCs are able to match, or even
outperform, human experts and more
conventional algorithms. A study by
Lietman et al28 concluded that ANNs
designed to detect VF defects could
also outperform accepted global
indices such as the mean deviation
and pattern Standard Deviation (PSD)
at specificities greater than 90%.
Li et al29 developed a DL network
that was trained on the probability
map of the pattern deviation image
to distinguish glaucoma from
healthy VFs. The network achieved a
diagnostic accuracy of 87.6%, higher
than glaucoma experts (62.6%) and
using traditional criteria such as
Advanced Glaucoma Intervention
Study (AGIS) (45.9%) and Glaucoma
Staging System 2 (GSS2) (52.3%). In
another study, Kucur et al30 reported
that a DL system trained with images
could identify early glaucomatous VFs
with an average precision of 87.4%.
76 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
AI for progression of the above studies reported the success DL approaches directly exploited
of AI in the assessment and prognosis of the visual information and extracted
functional damage functional damage, their performance glaucoma-related features from fundus
is variable due to the sheer subjectivity colour photographs.47-49 In a landmark
Presently there is no widely accepted involved in obtaining VF data (eg, multiethnicity study, Ting et al49
clinical index to predict glaucomatous patient factors, measurement noise, developed a DL network trained on
vision loss.31 Several research groups fixation losses).37 500,000 fundus photographs (125,189
have explored AI approaches to glaucoma images) that was capable of
increase the reliability of the clinical AI for the evaluation of discriminating glaucomatous fundus
prognosis in glaucoma. Brigatti et structural Damage due to photos with high confidence (AUC:
al32 developed an ANN trained on the Glaucoma 0.942; specificity: 87.2%; sensitivity:
VF threshold points, mean defect, Early AI-based studies assessed 96.4%). If successfully translated to
corrected loss, variance, false positive glaucomatous structural damage using clinics, the proposed DL-based system
and false negative ratios and patient age, data obtained from confocal scanning could cost-effectively diagnose and
produced a good agreement (sensitivity: laser ophthalmoscopy (CSLO), and stage glaucoma merely from optic
73% and specificity: 88%) with the scanning laser polarimetry (SLP) disc photographs. Li et al evaluated
experienced observer. Sample et al33 modalities. The clinical relevance a DL algorithm that showed a high
reported that standard MLCs predicted of these modalities has decreased in sensitivity (95.6%) and specificity
the development of abnormal fields, recent years because of advances in (92%) to detect referable Glaucomatous
on average, nearly 4 years earlier than ophthalmic imaging. Bowd et al38 Optic Neuropathy.50 The disadvantage
more traditional methods (StatPac-like) reported that MLCs, when trained was that high myopia caused false
in patients with ocular hypertension on global and regional optic disc negatives and physiological cupping
(OHT) thus proving helpful in the topographic parameters, offered a caused false positives. Al-Aswad et
early diagnosis. Studies exploiting significantly higher area under the al evaluated Pegasus (Visulytix Ltd.,
unsupervised techniques also concurred curve (AUC) when compared with more London UK), a DL system to detect
that the VF loss predicted by ANNs was standard methods. Moreover, studies glaucomatous optic neuropathy
comparable, or even better than, existing also concurred that MLCs trained on from color fundus photographs
clinical criteria.34 Similarly, Yousefi et the retinal nerve fibre layer (RNFL) and showed that it outperformed
al35 concluded that AI techniques could measurements from an SLP device 5 out of 6 ophthalmologists in the
identify patterns of progression earlier offered a diagnostic accuracy higher study.51 Pegasus is the AI system that
than more conventional methods. than the inbuilt software (GDx).39,40 is available free for use in the Orbis
Recently, Wen et al36 reported that DL Cybersight Consult Platform. NetraAI
networks could predict the future 24-2 With the advent of fundus colour (Leben Care Technologies Pte Ltd) is
Humphrey visual fields (HVF), up to 5.5 photography, studies have explored another AI that evaluates glaucomatous
years (figure 4), from a single HVF as the use of ANNs for the segmentation fundus photographs. Cerentini et al used
input. and classification of optic disc GoogLeNet52 to develop an automatic
photographs.41-46 Subsequently, many classification method to detect
It is also important to note that, while glaucoma in fundus images. Haleem et
al used a novel technique for automatic
Figure 4: A comparison between the actual (second column) and the AI-predicted (third boundary detection of optic disc and cup
column) HFVs as reported by Wen et al.36The input HFVs at different stages of glaucoma for to aid automatic glaucoma diagnosis
the AI algorithm are shown in the first column. AI, artificial intelligence; HVF, Humphrey from fundus photos.53 Thompson and
visual fields; MD, mean deviation; PMAE: point-wise mean absolute error. team was able to use deep learning
to measure NRR loss from optic
disc photos.54 Indian startup Kalpah
Innovations (Vishakapatnam, India)
released Retinal Image Analysis
– Glaucoma(RIA-G)55 cloud based
software in 2016 to analyse fundus
images to look for the likelihood of
glaucoma. It uses advanced image
processing algorithms to measure Disc
size, Cup size, CD ratio, NeuroRetinal
Rim Thickness, Disc Damage Likelihood
www.dosonline.org/dos-times DOS Times - Volume 26, Number 4, January-February 2021 77
Subspeciality-Glaucoma
Score (DDLS) and to look for violation included the RNFL and ganglion cell of AI systems by combining both the
of ISNT rule. plus inner plexiform layer thickness structural and functional evaluations
measurements, thickness probability of the eye. Brigatti et al74 assessed
Nowadays, OCT has emerged as the maps and the en face projection images. the performance of an ANN trained
standard for objective quantification In a population-based study (2701 on the ONH parameters (cup-to-disc
of glaucomatous structural damage of subjects; 135 glaucoma), Girard et al67 ratio, rim area, cup volume and RNFL
the ONH tissues.56 Huang and Chen57 developed a novel ‘Co-Training’ DL thickness) and the VF indices (mean
reported that ANNs successfully network to simultaneously segment defect, correct loss variance and short-
differentiated (AUC: 0.87) glaucomatous (figure 2A) and diagnose glaucoma term fluctuation). The network offered
and healthy eyes using OCT (figure 2B) from OCT images of the a higher diagnostic accuracy (88%)
measurements (RNFL thickness and ONH. The DL network first isolated when trained with both the structural
ONH parameters). Burgansky-Eliash et the individual neural and connective and functional information, as opposed
al58 showed that MLCs offered excellent tissues, and subsequently combined to only one of them (ONH parameters/
discriminatory power (AUC: 0.98) in the segmentation information with the VFs:80%/84%). Subsequent studies that
detecting glaucoma eyes from normal OCT images to identify glaucoma from combined the structural measurements
eyes using the OCT parameters obtained non-glaucoma subjects (AUC: 0.90). By from OCT,60,75 CSLO76-78 and SLP
from macula, peripapillary and ONH leveraging 3D structural information, parameters79 along with the perimetry
regions. The study also concluded that the DL network can discriminate evaluations also offered similar results.
MLCs were able to differentiate (AUC: glaucomatous eyes significantly better
0.85) early from advanced glaucoma than methods exploiting the RNFL In a slightly different hybrid approach,
eyes. Similar results were obtained by thickness values alone (figure 2B). Oh et al80 reported that an ANN trained
other research groups that used OCT Maetschke et al68 proposed a feature with a mix of ophthalmic (IOP, spherical
measurements.59-62 Although the above- agnostic approach that used a 3D DL equivalent refractive errors, vertical
mentioned studies reported the general network to classify glaucomatous and cup-to-disc ratio, presence of RNFL
success of AI systems in identifying healthy eyes directly from raw OCT defects) and systemic factors (sex, age,
glaucoma eyes using OCT parametric volumes (AUC: 0.94). Further, they also menopause, duration of hypertension)
data, their performance strongly concluded that the DL network focused could successfully differentiate
depended on the accuracy of the on the neuroretinal rim, optic disc (AUC: 0.89) between primary open-
automated measurements. For instance, area, and the lamina cribrosa and its angle glaucoma (POAG) subjects and
the presence of blood vessel shadows surrounding regions, while identifying a glaucoma suspects.
can adversely affect the performance glaucoma scan (figure 3). More recently,
of these tools, yielding incorrect RNFL in a multidevice, multiethnicity Other AI Approaches
thickness measurements.63 These study, Zhang et al69 reported that a DL Few studies have also explored the
artefacts are more pronounced in network could offer a fast (less than 1 potential of applying AI to genetic
glaucoma subjects since they already s) and simplified glaucoma diagnosis data. In the largest genome-wide
exhibit a thinner RNFL,64 thus limiting (AUC: 0.90) from just a single clinical association study conducted on nearly
the classification ability of AI systems. test (OCT scan of the ONH). Finally, a 140 000 participants, Khawaja et al81
Besides structural parameters, there number of studies have also used AI to identified 112 genomic loci (including
exists other visual information from detect glaucoma with varying success 68 novel loci) associated with IOP and
OCT images (speckle pattern, tissue from anterior segment OCT images and the development of POAG. Further,
reflectance) that are associated with measurements (AUC ranging from 0.85 they developed a regression model that
the progression of glaucoma.65 Thus, to 0.96).70-73 predicted POAG with an AUC of 0.76
by better exploiting the information based on these loci. Burdon et al82 used
contained within OCT image; it is Niwas et al also evaluated a fully both regression and ANN models and
feasible to increase the diagnostic automated model to classify angle concluded that a combination of disc
power of the instrument in glaucoma closure glaucoma from Anterior parameters, IOP and POAG-associated
clinics. Segment OCT (AS-OCT) scans and loci could improve the accuracy of
showed an accuracy of 89.2%.73 POAG risk prediction models, thus early
Muhammad et al66 also proposed a treatment and prevention of blindness.
hybrid approach that used a CNN Hybrid AI approaches
to extract features from widefield Given the inherent subjectivity Discussion
(9×12 mm) OCT scans that were later of functional assessments and the In this review, we discuss the role of
classified by an RF classifier to predict variability in structural measurements, AI in the diagnosis and prognosis of
the existence of glaucomatous damage research groups have attempted to glaucoma using functional or/and
(AUC: 0.94). The extracted features increase the discriminatory power structural evaluations. While early
78 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
studies relied on simple MLCs or glaucoma increases the likelihood of cumbersome. Besides, the subjective
ANNs to detect glaucomatous eyes incorrect management of these patients. definitions for suspect/moderate
using parametric data, modern DL AI tools for the segmentation and phenotypes could compromise the
systems have successfully exploited enhancement of ONH tissues could help integrity of training data, eventually
high-dimensionality image data, clinicians to better visualise and model affecting the performance of such tools.
thus increasing the diagnostic power the 3D structural information in OCT
of ocular imaging modalities such images for each patient, thus improving The ‘black-box’ nature of AI algorithms
as fundus photography and OCT in the reliability of the prognosis offered. has offered resistance to its clinical
clinics. The use of AI algorithms in Eventually this could open doors for a adoption. AI algorithms discriminate
clinics may be viewed as a tool to assist range of tools for the clinical forecasting, based on the correlations/patterns
clinicians, but not to replace them. personalized pharmacological/surgical they infer from the training data.
AI methods can help speed up the recommendations and monitoring These correlations may or may not be
triage process by collating data from glaucoma therapeutic efficacy. in concurrence with the theoretical
multiple tests, detecting abnormalities cause. When exposed to high-
and offering relevant referrals. Thus, There exist several challenges in the dimensionality data (eg, a combination
AI systems can help create a clinically clinical translation of AI tools in of ophthalmic and non-ophthalmic
conducive environment that better uses clinical practice. First, the performance parameters), the algorithm might
specialised resources, reduce workload of these tools primarily depends on pick up intrinsic patterns in the data
for clinicians, minimise diagnostic the quality of training data (quality that might correlate to glaucoma, but
errors leading to incorrect treatment of images, presence of artefacts). might not be clinically correct. For
and improve the overall quality of Furthermore, a large (>100 000 images) instance, given the strong correlation
ophthalmic care for patients with and diverse training set with a good mix in the prevalence of glaucoma with
glaucoma. of ophthalmic (severity of glaucoma, demographics (ethnicity, age, gender),
presence of other conditions which the AI algorithm might learn to
With its ability to extract meaningful can differentiate it from other clinical identify pathology merely based on
features from complex modalities, diagnoses) and non-ophthalmic the demographics and neglecting the
modern AI methods can help in the factors (such as- age, ethnicity, race) ophthalmic parameters. The chances
discovery of new biomarkers to improve is generally recommended to ensure of identifying such clinically irrelevant
our current understanding of glaucoma. clinical robustness. Curating such a correlations increase when dealing
This could be useful for the early training set in practice is expensive and with high-dimensionality data (eg, OCT
detection of glaucoma and to promote daunting. images), if the algorithm is not designed
research and development into new and validated carefully, thus leading to
drugs and treatment. Thus, a synergy Secondly, while all the above studies excess false positives and false negatives.
between AI systems and clinicians discussing the use of AI to assess The use of such visualisation tools is
could lead to mutual advancements in glaucoma seem encouraging, it must still in its infancy and development of
both glaucoma research and clinical be noted that the AUCs are extremely such tools is crucial for the widespread
practices. subjective and cannot be used to clinical adoption of AI algorithms.
directly compare different studies due
Newer telemedicine-based screening to the following reasons. Given the performance subjectivity
methods, especially in the era of of these tools due to the variability in
COVID-19 has offered the benefits of The prevalence of glaucoma, its type image quality and device, a clinical
early detection, reduced travel times, and severity varies among different verification of the results is required
increased specialist referral rates, thus regions, ethnicities, age and gender. before the final decision is made. Clear
saving costs for both the individual and medicolegal guidelines and a diagnostic
the healthcare system. Incorporating Asymtomatic nature of the disease, may pipeline involving both the AI systems
AI systems with the ocular imaging change what constitute normal and and clinicians to minimise errors are
modalities used in telemedicine might glaucoma populations across countries. essential for an economically feasible
be a long-term and cost-effective adoption and increased acceptability of
solution to increase screening efficacy, While longitudinal predictions from these tools.
and to monitor patients in primary structural analysis of OCT images
care and community settings where might help in the prognosis and The approval of regulatory bodies such
resources and access to specialists are even early diagnosis of glaucoma, the as the Food and Drug Administration
limited. development of such an AI system required for the clinical use of these
is a clinical challenge because the diagnostic tools is likely to be difficult.
The lack of a widely accepted clinical recruitment and follow-up of a This is due to the fact that the required
reference to predict the progression of large cohort is very expensive and performance for clinical acceptance is
www.dosonline.org/dos-times DOS Times - Volume 26, Number 4, January-February 2021 79
Subspeciality-Glaucoma
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67. Girard MJA, Chin KS, Devalla SK. Deep 74. Brigatti L, Hoffman D, Caprioli J. Neural Genet 2018;50:778–82.
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glaucomatous eyes. Invest Ophthalmol
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et al. A feature agnostic approach for DNB Resident, Department of Ophthalmology,
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82 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Glaucoma and Myopia
Shweta Tripathi1, M.M.Srinivasan2
1. Senior Consultant Glaucoma Services , Indira Gandhi Eye Hospital and Research Centre, Lucknow
2. Ex Professor Regional Institute of Opthalmology, Chennai
Abstract: IOP is the most significant and only modifiable risk factor in Glaucoma , However Primary open angle glaucoma has
many risk factors of which myopia is significant with its masquerading features in the diagnosis .
The diagnosis of Myopic Glaucoma warrants early management to delay the disease progression.
Key words : (open angle glaucoma ,Myopia ,Myopic Glaucoma)
Glaucoma is the leading cause of The increase in intraocular pressure pressure or vasospasm20 Thus, although
irreversible blindness globaly. The in POAG can be caused by an increase elevated IOP is still considered as the
global prevalence of glaucoma for in the secretion of aqueous humour major risk factor of glaucoma, there has
population aged 40–80 years is 3.54% or a reduction in its outflow16. The been an increase in evidence supporting
. The prevalence of POAG is highest in pathogenesis of POAG is still poorly significant roles for vascular risk factors
Africa and the prevalence of PACG is understood with two major theories in the pathogenesis of glaucoma.
highest in Asia. In 2013, the number being proposed: ‘the mechanical Although the mechanisms responsible
of people (aged 40–80 years) with theory’ and ‘the vascular theory’ for the for the link between glaucoma and
glaucoma worldwide was estimated initiating mechanisms of POAG. myopia are poorly understood, it has
to be 64.3 million, increasing to 76.0 The mechanical theory hypothesizes been postulated that the optic nerve
million in 2020 and 111.8 million that an elevated IOP compresses the head in myopic eyes may be structurally
in 20401. The risk and subtypes of structure in and around the optic more susceptible to glaucomatous
glaucoma vary among different races nerve head, disturbing the axoplasmic damage because of the alterations
and countries. transport within the nerve fibers,which in connective tissue structure and
Open angle glaucoma is a progressive in turn leads to the death of RGCs arrangement21.
neurodegeneration of retinal and their axons further, resulting in The different anatomical factors in
ganglion cells (RCGs) and their axons thinning of the neuroretinal rim and myopic eyes such as: longer axial
characterized by a specific pattern excavation of optic nerve head 17. lengths ,longer vitreous chamber depths
of visual field and optic nerve head Based on this theory, lowering IOP ,deformed lamina cribrosa contribute
damage2-4. Elevated intraocular pressure by pharmacologic and surgical to higher susceptibility to mechanical
is a well-known major risk factor for interventions can be included as damage.22-23 The mechanical stress on
POAG. In addition, there is growing efficient treatment options for the axons of the retinal ganglion cells
evidence that other risk factors like age, prevention of further damage to leads to compromised ocular blood
gender, race, refractive error, heredity the optic nerve system clinically flow and ocular ischemia. The increased
and systemic factors may play a role in appreciated as slowing down the risk of development of glaucomatous
glaucoma pathogenesis. Many studies progression of visual field loss18-19. change may be related to the already
found that high myopia has been In the vascular theory, glaucomatous reduced retinal nerve fiber layer (RNFL)
associated with POAG5. optic neuropathy is considered to be thickness in myopic eyes21.
An association between myopia and a consequence of insufficient blood Several theories have been proposed
primary open-angle glaucoma has been supply because of either increased IOP to explain a link between myopia and
recognized for decades.6-8 Myopia has or other causes that reduce ocular blood POAG. The association between myopia
also been found to have an influence on flow, such as elevated systemic blood and POAG has been thought to be due
intraocular pressure (IOP)9-15
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Subspeciality-Glaucoma
to a variety of mechanisms, including structural change in glaucoma is based Studies showed that, for a given IOP in
increased susceptibility of the optic on assessment of the RNFL. Numerous eyes with POAG, optic nerve damage
nerve head to be damage by raised IOP studies have confirmed that RNFL appears to be more pronounced in
and the increased effect of shearing measurement is sensitive for detection highly myopic eyes with large optic
forces in optic nerve head damage. of glaucoma, and the extent of RNFL discs than in non–highly myopic eyes
An important approach to detect early damage correlates with the severity of
functional deficit in the visual field.
Clinical Pointers in Myopic Glaucoma(Myopic optic neuropathy +Glaucomatous optic neuropathy)
Myopic Neuropathy Myopic optic disc Myopic glaucoma Myopic glaucoma Optical coherence
and visual field and disc tomography In
defects near the hemorrhage Myopic Glaucoma
fixation point
In myopic neuropathy Glaucomatous optic Myopic glauco- One of the major Thinning of gan-
discs can be classified matous eyes with risk factor of glau- glion cell complex
Visual field defects can occur into four types by disc RNFLD in the pap- coma progression (retinal nerve fiber
in the absence of typical morphology: illomacular bundle is the presence of layer +retinal gangli-
fundus findings due to: i. Focal ischemic type: could be more sus- disc hemorrhage on cell layer +inner
i. Changes in the fragility of ceptible to a visual : The incidence of plexiform layer in
disc rim notching field defect near the which is lower in the papillomacular
the supporting tissue in ii. Myopic type: tempo- fixation point at an myopic eyes due bundle using OCT
the lamina cribrosa . early stage hence, to difference in can be used for glau-
ii. Dynamic imbalance due ral tilting of the disc myopic glaucoma pa- structural changes comatous myopic
to structural changes in iii. Senile sclerotic type tients should be man- in lamina cribrosa eyes.
the surrounding of the : peripapillary cho- aged at early stage be- in myopic and non
rioretinal atrophy fore the development myopic eyes.27
optic nerve head. with shallow cup- of impaired visual
ping acuity and central vi-
ii. Scleral curvature tempo- iv. General enalarge- sual field defects .
ral to the optic disc is as-
sociated with the progres- ment type : concen-
sion of the visual fields in
myopic eyes.24 tric dip cupping
iv. The mean retinal sensitiv-
ity decrease as the axial
length elongates in myo-
pic eyes. 25
Glaucomatous PPA and
myopic conus are often
confused as same entities,
a significant correlation
between the enlarged area
of the PPA and the visual
field progression have been
reported : The myopic conus
has only retinal nerve fiber
layer &no overlying choroid.
In the region of PPA retinal
layers and Bruch’s membrane
are there except the Retinal
Pigment Epithelium.26
84 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
P., Suoranta L., Teir H., Uusitalo H.,
Vainio-Jylhä E., Vuori M.L. The finnish
evidence-based guideline for open-angle
glaucoma. Acta Ophthalmol. Scand.
2003;81(1):3–18
5. Chen SJ, Lu P, Zhang WF, Lu JH. High
myopia as a risk factor in primary open
angle glaucoma. Int J Ophthalmol.
2012;5(6):750-3.
6. Knapp A. Glaucoma in myopic eyes.
Arch Ophthalmol 1926; 55:35–7.
7. Mo¨ller HU. Excessive myopia
and glaucoma. Acta Ophthalmol
1948;26:185–93.
8. Fong DS, Epstein DL, Allingham RR.
Glaucoma and myopia: are they related?
Int Ophthalmol Clin 1990;30:215–8
9. Tomlinson A, Phillips CI. Applanation
tension and axial length of the eyeball.
Br J Ophthalmol 1970;54:548–53.
Fig 1 Schematic representation of Myopic tilted disc 10 Abdalla MI, Hamdi M. Applanation
ocular tension in myopia and
emmetropia. Br J Ophthalmol
1970;54:122–5.
11 Seddon JM, Schwartz B, Flowerdew
G. Case–control study of ocular
hypertension. Arch Ophthalmol
1983;101:891–4.
12. David R, Zangwill LM, Tessler Z, Yassur
Y. The correlation between intraocular
pressure and refractive status. Arch
Ophthalmol 1985;103:1812–5.
13. Linner E. The association of ocular
hypertension with the exfoliation
syndrome, the pigmentary dispersion
syndrome and myopia. Surv Ophthalmol
1980;25:145–7.
Fig 2: OU Myopic Disc 14 Quinn GE, Berlin JA, Young TL, et al.
Association of intraocular pressure and
myopia in children. Ophthalmology
1995; 102:180–5.
Conclusion of glaucoma and projections of 15. Ganley JP. Epidemiological aspects of
There are many myopic glaucoma cases glaucoma burden through 2040: a ocular hypertension. Surv Ophthalmol
in which the glaucoma and myopic systematic review and meta-analysis. 1980;25:130–5
changes both can be present at the Ophthalmology. 2014 Nov;121(11):2081-
same time. All opthalmologists should 90. 16 Lutjen-Drecoll E, Kruse FE. Primary open
treat such cases during early stages 2. Gandolfi S. Il Glaucoma. Roma, Italia: angle glaucoma. Morphological bases for
to prevent a rapid progression of the Mattioli Editore; 2005. the understanding of the pathogenesis
blinding disease and thus ensuring an 3. 2.European Glaucoma Society. and effects of antiglaucomatic
improved quality of life to the patient . Terminology and guidelines for
glaucoma. 3rd ed. Savona: Italia: Dogma substances. Ophthalmologe.
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1. Tham YC, Li X, Wong TY, Quigley HA, E., Forsman E., Friberg K., Kaila M., 17. Flammer J, Orgul S, Costa VP, Orzalesi
Aung T, Cheng CY. Global prevalence Klemetti A., Mäkelä M., Oskala P., Puska N, Krieglstein GK, Serra LM, Renard JP,
Stefánsson E. The impact of ocular blood
flow in glaucoma. Prog Retin Eye Res.
2002;21(4):359–393
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Subspeciality-Glaucoma
18. Higginbotham EJ. Ocular hypertension Ophtalmic pysiolopt13:41-47 27. Jong Chul Han, Seok Ho Cho, Dae
treatment study. Arch Ophthalmol. Yong Sohn, Changwon Kee; The
2009;127(2):213–215. 23. Jonas JB, Dichtl A. Optic disc Characteristics of Lamina Cribrosa
morphology in myopic primary open- Defects in Myopic Eyes With and
19. Keltner JL, Johnson CA, Cello KE, angle glaucoma. Graefes Arch Clin Exp Without Open-Angle Glaucoma. Invest.
Bandermann SE, Fan J, Levine RA, Kass Ophthalmol. 1997 Ophthalmol. Vis. Sci. 2016;57(2):486-49
MA, Gordon MO, Ocular Hypertension
Treatment Study Group Visual 24. Ohno-Matsui K, Shimada N, Yasuzumi Corresponding Author:
field quality control in the Ocular K, Hayashi K, Yoshida T, Kojima A,
Hypertension Treatment Study (OHTS) Moriyama M, Tokoro T. Long-term Dr Shweta Tripathi
J Glaucoma. 2007;16(8):665–669. development of significant visual field Senior Consultant Glaucoma Services ,
defects in highly myopic eyes. Am J Indira Gandhi Eye Hospital and Research
20. Barnett EM, Fantin A, Wilson BS, Kass Ophthalmol. 2011 Aug;152(2):256-265. Centre, Lucknow
MA, Gordon MO, Ocular Hypertension
Treatment Study Group The incidence 25. Michael G. Quigley, Ian Powell, Walter
of retinal vein occlusion in the Wittich; Increased Axial Length
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Decreasing AMD Risk in Myopia. Invest.
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myopia as a risk factor in primary open 3857.
angle glaucoma. Int J Ophthalmol.
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peripapillary atrophy is associated with
22. Scott R.Groverson(1993).Structural progressive glaucoma. Ophthalmology.
model for emetropic and myopic eye . 1998 Aug;105(8):1541-5
86 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Ocular Perfusion Pressure:
Bridging the gaps in Glaucoma
Management
Amit Mehtani MS, DNB, Jatinder Singh Bhalla MS, DNB, MNAMS, Prathama Sarkar MS, DNB,
Harish Chandar Gandhi MS, Arti Rajak DNB, Mohit Kumar Gupta DNB
Department of Ophthalmology , DDU Hospital, New Delhi
Abstract: Glaucoma is one of the leading causes of blindness in the world. Most of the treatment approaches are based on the
concept of lowering IOP. However, it has been seen that vascular supply also plays a significant role in the pathogenesis of
glaucoma. The low ocular perfusion pressure (OPP), blood pressure and intraocular pressure have been found to be associated
with glaucoma development and progression. This article intends to emphasise upon the role of OPP, as a modifiable risk factor
in the management of glaucoma.
Key words : Ocular perfusion pressure, mean ocular perfusion pressure, systolic ocular perfusion pressure, diastolic ocular
perfusion pressure, autoregulation, open angle glaucoma, normal tension glaucoma
Methodology which was expected to increase up to and the nutritional needs of the tissue,
76 million in 2020 and 111.8 million in for its functioning. To date, the actual
We searched PubMed for studies 20401. relationship that exists between reduced
published in English between 1970 Elevated intra ocular pressure (IOP) OPP and glaucoma is not clear. The
and November 2020, incorporating the is known to be a major risk factor for hypothesis states that the reduction of
general search term “ocular perfusion the disease, and at present, mainly, OPP along with vascular dysregulation
pressure” with more precise search decreasing the IOP is the only proven leads to subsequent ischemia of the
terms relevant to subheadings — e.g., means of halting the development. optic nerve head further contributing
“Mean ocular perfusion pressure,” However, the paradox is that 90% to the glaucomatous damage.
“systolic ocular perfusion pressure,” of patients with elevated IOP never
“diastolic ocular perfusion pressure,” develop significant damage to the optic Ocular Perfusion Pressure
“nocturnal dips,” “blood pressure and nerve head and at least 33% of patients The term ocular perfusion pressure
OAG,” “MOPP,” “SOPP,” DOPP,” etc. with open angle glaucoma (OAG) never refers to the difference between the
References from identified studies have have documented elevations2. arterial BP and the intraocular pressure
been reviewed and included if deemed These findings suggest that there are (IOP), which is considered a substitute
appropriate, valid and scientifically other risk factors too that play a major for the venous pressure the net pressure
important. If referenced in a selected role in the pathogenesis of glaucoma. gradient causing blood to flow to the
English paper, we contemplated papers Nowadays, the emphasis has been eye. It is the driving force for ocular
in other languages too. We shifted towards the role of vascular blood flow. It may act as a risk factor
preferentially selected papers that have factors on the onset and progression and/or progression factor for OAG.
been published in the last 20 years, of glaucoma. Studies have shown that
but we have included relevant older reduced ocular perfusion pressure Table 1: Calculation of OPP
references. (OPP) is an important reason in the
pathogenesis of the disease. This Mean OPP 2/3 [diastolic BP + 1/3
Introduction relation is more commonly found (MOPP) (systolic BP – diastolic
in the diagnosed cases of glaucoma BP)] – IOP
Glaucoma is a multifactorial optic with lower IOP. Hence, it is very
neuropathy that causes a characteristic much required to assure an adequate Systolic OPP Systolic BP – IOP
acquired loss of retinal ganglion perfusion with sufficient blood flow (SOPP)
cells (RGC) and atrophy of the optic for the maintenance of the metabolic
nerve. The number of people suffering Diastolic Diastolic BP – IOP
from glaucoma in the year 2013 was OPP (DOPP)
estimated to be 64.3 million worldwide,
BP- blood pressure IOP- Intra-ocular pressure
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Subspeciality-Glaucoma
In table 1, it can be seen that the change change in resistance of vessels to keep increased cerebral perfusion pressure.
in the OPP is dependent on both the the tissue ocular blood flow and the Chronic hypertension affects ocular
BP and IOP of the patient ie. OPP is metabolic activity stable. Evidence autoregulation differently from
directly proportional to the change in suggests that the retinal capillary cerebral blood flow, to produce a
the BP and indirectly proportional to bed has autoregulation, whereas it is narrower autoregulatory plateau. A
the IOP changes. Since MABP (mean absent in choroidal beds and thus can narrower autoregulatory range might
arterial blood pressure) is significantly render the photoreceptors susceptible arise due to atherosclerosis, such that
higher than IOP, and the normal range to vascular damage. If the auto- blood vessels are less able to change
varies within 40-60 mm Hg within each regulatory procedure is defective or if their calibre in response to stimulation
cardiac cycle; OPP fluctuation is more the minimum perfusion pressure falls by vasoactive factors5. There may be
sensitive towards the variation in blood below a threshold beyond which the aberrant production of vasoactive
pressure rather than IOP. Thus, a 10-mm metabolic activity is stopped, periods peptides involved in autoregulation.
Hg change in systolic BP will lead to a of inadequate perfusion may happen
2.2-mm Hg change in mean OPP, while to result in ischemia. If the ischemia is Evidence based studies
a similar 10-mm Hg change in diastolic prolonged, it will result in local tissue supporting the role of OPP in
BP will cause a 4.4-mm Hg change in necrosis and ganglion cell apoptosis. glaucoma
mean OPP. So, patients with perfusion pressure Various studies have been conducted
This calculation has several other lower than 50 mmHg are at greater on the relationship between BP,
assumptions too, ie. (a) venous pressure risk for developing or worsening POAG IOP, OPP and glaucoma. The table 2
is equivalent to IOP, (b) brachial whereas at 30 mmHg the risk is 4 times highlights the key design of the studies.
artery pressure is a good surrogate for greater3. However, five of the mentioned studies
ophthalmic artery pressure, and (c) the are considered as golden studies in this
difference between the brachial and Vascular dysregulation and regard, ie. Baltimore Eye Survey10,
ophthalmic artery pressure is the same Egna-Neumarkt Study11, Proyecto
in the diseased and normal eyes. glaucoma VER12, Los Angeles Latino Eye Study13
and Barbados Eye Study12.
Theories associated with OPP Abnormalities in autoregulation
The mechanical theory proposes the fact have been divided into primary and The Baltimore Eye Survey10 was
that an elevated IOP leads to changes in secondary vascular dysregulation conducted in European and African
the structure of axons to the extent that (without or with underlying disease, ancestry in Baltimore, Maryland. The
they are compressed leading to their respectively). The presence of secondary study highlighted the fact that lower
death. vascular dysregulation could increase OPP was strongly associated with a
The vascular theory postulates that if the the vulnerability of the optic nerve to higher prevalence of POAG. Patients in
perfusion pressure is very low, enough small changes in IOP, blood pressure and the lowest category of DOPP (<30 mm
blood doesn’t reach the optic nerve, metabolic needs. This occurs if vascular Hg) were found to have a 6-fold higher
ultimately causing its death. dysregulation reduces the effectiveness risk of having glaucoma compared
The fluctuation theory asserts that it is of autoregulation. Thus, the same with those whose DOPP was >50 mm
important to take into consideration the change in OPP can cause a greater Hg.
diurnal fluctuations of IOP, rather than reduction in blood flow. Autoregulation
recording single pressure recordings confers a wide ‘zone of safety’ and The Egna-Neumarkt Study11 conducted
which are taken months apart. thus an increased capacity to cope in the northern Italy, stated that
The neurogenic theory advocates with changes in the OPP. On the other persons with low DOPP were at a higher
that different people have different hand, the absence of autoregulation risk for having glaucoma. Patients with
thresholds of vulnerability to all means that smaller changes in the DOPP <60 mm Hg had a 2.5-fold higher
pressures, and damage to the optic nerve OPP are needed to push blood flow risk for glaucoma compared with those
is even more than what is found in the outside of the ‘normal range.’ Systemic with DOPP >76 mm Hg.
visual field defects, even in individuals hypertension alters the autoregulation
with “normal” pressures. in systemic circulation, via endothelial Proyecto VER study12 found that
cell damage/ dysfunction and abnormal participants with DOPP <50 mm Hg
Role of autoregulation release of vasoactive substances. Harper had a 4-fold higher risk for having
In healthy subjects, the ocular blood and Bohlen4 found that autoregulatory glaucoma than those with DOPP >80
flow is auto-regulated through the capacity of cerebral blood flow in mm Hg.
spontaneously hypertensive rats is
rightward shifted to higher pressure, The Los Angeles Latino Eye Study13
consistent with an effort to compensate found that in comparison to the people
for the potential hyperaemia during whose DOPP was between 51- and 60-
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Subspeciality-Glaucoma
Table 2: Key design of various studies on OPP and glaucoma
Study Type of study No. of participants Year Population
1992 Sweden
Early Manifest Longitudinal: Incidence Study 255
Glaucoma Trial6 1994 Afro-Caribbeans
1990 Ommoord, a district of Rotterdam
Barbados Eye study12 Longitudinal: Incidence Study 4709 2000 Non-Hispanic Whites
Rotterdam7 Longitudinal: Incidence Study 7983 2001 Hispanics
2001 Adult Chinese
Egna-neumarkt Cross- sectional: Prevalence study 4279 2004 Tajimi (in Japan)
Study11 2004 Latinos/Hispanics
Proyecto VER12 Cross- sectional: Prevalence study 4774 2007 Thessaloniki, Greece
2008 Malay
Beijing eye study8 Cross- sectional: Prevalence study 4439
Tajimi9 Cross- sectional: Prevalence study 3280
Los Angeles Latino Cross- sectional: Prevalence study 6357
Eye Study13
Thessaloniki15 Cross- sectional: Prevalence study 2554
Singapore Malay Cross- sectional: Prevalence study 3280
Study16
mm Hg, those whose DOPP was below the ganglion cells increase towards the nucleus to the ganglion cell body. This
40 mm Hg had a 1.9-fold higher risk for hypoxic and metabolic stress. Studies17 loss initiates the apoptotic cascade.
glaucoma. In fact, low DOPP, SOPP, and have found that with ageing, there
MOPP were all highly associated with is reduction in the ocular blood flow According to the vascular mechanism,
the risk for glaucoma in this study. progressively along with insufficient the elevated IOP causes distortion of
capacity for auto regulation. Animal the lamina cribrosa which leads to the
The Barbados Eye study14 reported that studies have also showed that older compression of the blood vessels at
individuals with a low baseline SOPP, rats are less capable in maintaining the the optic nerve head, causing regional
DOPP, or mean OPP had an increased blood flow in comparison to the young hypoxia. If the auto regulation
risk of developing OAG. Specifically, rats in response to evaluated IOP18. mechanism fails in sustaining the
those with an SOPP lower than 101 mm normal blood flow, it will cause
Hg, a DOPP below 55 mm Hg, or a mean The Barbados study has shown a relative ischemia leading to cellular injuries.
OPP under 42 mm Hg at baseline had risk ratio (RR) of 1.02 to 1.05 per year of
a 2.6-, 3.2-, and 3.1-fold increased risk, developing POAG after 60 years of age. In the study conducted by Kim et al.20,
respectively, of developing glaucoma The EMGT study6 has also supported it was found that OAG patients with
at 4 years. Furthermore, subjects with the same stating that older age is a risk baseline IOP > 21 mmHg (P = 0.019) had
an SOPP of 98 mm Hg or less, a DOPP factor for OAG. The Rotterdam Study7 significantly lower OPP in comparison
of 53 mm Hg or less, and a mean OPP found a hazard ratio of 1.074 with to the controls (P < 0.001), but such
of 40 mm Hg or less at baseline had a increasing age in the development of difference in OPP was not significant
2.0-, 2.1-, and 2.6-fold increased risk, OAG. between OAG patients with baseline
respectively, of developing glaucoma IOP of ≤21 mmHg and controls
at 9 years. (b) IOP and OAG (P = 0.996).
Various theories have been discussed
Variables emphasised in in brief earlier regarding the onset Whatever may be the underlying cause,
these studies and progression of glaucoma. The all the major studies have concluded
mechanical theory states that IOP that a higher baseline IOP is one of
All the above-mentioned studies have elevation induces remodelling and the major risk factors in OAG. The
reviewed various factors associated deformation of the lamina cribrosa, Rotterdam Study7 concluded that the
with OPP and OAG. (Table 3) leading to mechanical compression of OPP appeared to be associated with
ganglion cell axons at the ONH, causing incident OAG. This was due to the fact
(a) Age and OAG impairment in the anterograde and that the IOP, a strong risk factor for
Due to the age-related changes, in retrograde axoplasmic transport19. This OAG, is part of the OPP, rather than that
order to maintain the normal blood leads to interruptions of the neutrophils OPP as an independent OAG risk factor
flow against the fluctuating OPP transport from the lateral geniculate itself.
(autoregulation), the vulnerability of
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Subspeciality-Glaucoma
Table 3: Studies showing the effect of various vascular variables on OAG
Study BP and OAG Mean OPP and OAG DOPP and OAG SOPP and OAG
SOPP < 101 mm Hg
Barbados eye Decreased risk Mean OPP < 42 mm Hg DOPP < 55 mm HG associated with 2.6-fold
study12 associated with 3.1-fold associated with 3.2-fold increase in developing
increase in developing increase in developing glaucoma
glaucoma glaucoma
SOPP < 80 mm Hg
Early Manifest Decreased risk associated with 2.5-
Glaucoma Trial6 fold increase in OAG
prevalence
Rotterdam7 Increased risk
Egna-neumarkt Increased risk DOPP < 68mm Hg
Study11 associated with 3-fold
increase in OAG
prevalence
Proyecto VER12 Increased risk DOPP < 50 mm HG
associated with 4-fold
increase in OAG
prevalence
Los Angeles Both high systolic and Mean OPP < 50 mm Hg DOPP < 40 mm HG
Latino Eye Study13 low diastolic BP increase associated with 3.6-fold associated with 1.9-
the risk increase in developing fold increase in OAG
glaucoma prevalence
Baltimore eye Age-dependent; Reduced DOPP < 30 mm HG
survey10 risk for younger, associated with 6-fold
increased risk for older increase in OAG
prevalence
(c) MOPP and OAG that patients with OAG had significant for development of OAG in patients
In The Early Manifest Glaucoma Trial6, fluctuations in the MOPP. with low DOPP (<55 mmHg). When
The Barbados Eye Study14, and The Blue these patients were further followed
Mountain Eye Study21; OPP was adjusted (d) SOPP and OAG up for 9 years, patients with lowest
for IOP, but no significant association The Blue Mountains Eye Study21 found 20% of DOPP had 2.2 times more
was found between MOPP and OAG. a marginal significance for SOPP in chances of developing OAG. Similarly,
The Singapore Malay Eye Study16 stated relation with OAG (P < 0.05). The The Proyecto VER12, The Baltimore Eye
that low MOPP is an independent risk Barbados study14 reported that low Survey10, The Singapore Malay Eye
factors for OAG development in their SOPP was associated with a higher risk Study16, The Egna-Neumarkt Study11,
ethnic Malays. of developing glaucoma at 4 and 9 years and Rotterdam Study7 too, found a
of follow-up. The Los Angeles Latino reduced DOPP to be a risk factor for
The circadian rhythm has a prominent Eye Study13 stated that SOPP < 80 mm OAG. For the relationship between
influence on blood pressure or IOP, Hg was found to be associated with 2.5- OPP and ocular hypertension, The
which is overlooked by most of the fold increase in OAG prevalence. Singapore Malay Eye Study16 found
studies as they have mostly taken into that only DOPP had a protective effect
account only a single measurement, (e) DOPP and OAG population-based (P < 0.0008).
that too during day time. This in turn Various (f) Hypertension and OPP
overlooks the influence of the nocturnal Population-based studies have
dip in the BP. It has been seen in the epidemiological studies have shown a invariably found a strong association
studies that fluctuations in IOP cause strong association between low DOPP between high blood pressure and IOP.
more damage to the optic disc than an and increased prevalence of OAG. Low Each 10 mmHg rise in systolic blood
increase in IOP22. In a study23 where DOPP is an important factor in the pressure is associated with only a small
evaluation of the diurnal fluctuations of progression of glaucoma, as most of increase in IOP (approximately 0.27
IOP and MOPP was done in participants the tissue perfusion occurs during the mmHg). The physiological basis of the
with and without OAG, it was found diastole phase24. In the Barbados Eye
Study12, there was a relative risk of 3.2
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Subspeciality-Glaucoma
relationship between blood pressure vascular resistance and compromised C. Nocturnal dippers
and IOP remains unclear. vascular autoregulation, along with the D. Effect of anti-hypertensives.
impairment of the nutrient exchange
This increase in the blood pressure in the capillary beds of the optic nerve (h) Normal Tension Glaucoma (NTG)
and IOP may be because of the rise in head25. This argues for the use of OPP, and OPP
the sympathetic tone which is age- rather than IOP or blood pressure alone,
related. Another theory states that the as a primary risk factor for glaucoma. During sleep, there is a decrease in the
ciliary artery pressure may get elevated It suggests that BP should be assessed activity of the sympathetic nervous
because of the increase in the blood in each OAG patient and its proper system, which causes a dip in the BP
pressure, which may in turn increase management is very much required in nocturnally. This nocturnal dip is seen
the ultrafiltration of the aqueous the treatment of OAG. in both normotensive and hypertensive
production, leading to an increase in individuals. However, there are around
the IOP. The increase in the arterial (g) Anti-hypertensives and OAG 10% of patients having a decrease of
pressure produces small elevation in Thessaloniki Eye Study15 reported 10% or less in the blood pressure at
the venous pressure, causing reduction that overly aggressive treatment with night. These patients are known as non-
of the aqueous clearance, which finally antihypertensive medications (too rapid dippers. This occurs due to autonomic
acts as a causative factor for higher or too large blood pressure lowering), dysfunction or due to use of steroids
IOP25. The blood pressure and open- which produces a large drop in the OPP, or poor sleep quality or during post-
angle glaucoma have a complicated increases the risk for glaucoma. The menopausal phase. Higher blood
relationship. The BP influences both cause of such an association is related to pressure at night increases the risk of
IOP and OPP. Long-standing cases an increased resistance in arterioles or cardiovascular mortality, while extreme
of hypertension may also have a capillaries in essential hypertension. If dippers are protected against end-organ
compromised peripheral vascular high blood pressure is treated without damage Non-dippers have a 20% higher
capacity and auto-regulation leading to altering capillary resistance, this risk of cardiovascular mortality,28 or the
progression of glaucoma25. will produce greater levels of tissue non-dipping pattern may itself cause
hypoxia. Consistent with this theory, problems for unknown reasons.
Few studies have reported a significant aggressive treatment of hypertension
correlation between glaucoma can cause serious harm not only to the Measurements of IOP and BP should be
and high blood pressure and other eye but also to the heart and brain. The taken in both seated and supine position
between glaucoma with low blood Rotterdam Study7 found that calcium as higher readings of IOP are recorded in
pressure (Table 3). Despite the positive channel blockers decrease the BP the supine position due to an increase in
correlation between blood pressure without affecting the IOP but lowers the episcleral venous pressure, while BP
and IOP, the actual change in IOP the OPP significantly, thus, increasing noted to be lower in the supine position
with increasing blood pressure is the risk of OAG progression. The beta- as a result of a drop in cardiac output29.
small. Therefore, it is unlikely that the blockers however have showed no The change in OPP depends on the
increased risk of developing glaucoma particular trend. However, some studies magnitude of each of these changes. Liu
associated with high blood pressure can have reported that consumption of et al. reported that IOP increases in the
be attributed to a blood-pressure-driven ACE-I may be related to a higher risk supine position approximate 6 mmHg
IOP elevation. Los Angeles Latino Eye of POAG, and B-blocker consumption in both normal and glaucomatous
Study13 shows that both low diastolic could decrease the risk of development patients30. In addition to an increase
and high systolic blood pressure are of glaucoma26,27. in IOP, postural changes can influence
associated with an increased prevalence OPP through BP, as moving from the
of open-angle glaucoma. Relationship Plausible hypothesis in seated position to the supine position
between glaucoma prevalence and hypertensives for OAG can result in a drop in systemic BP by 20
diastolic blood pressure is ‘U’ shaped. It mmHg – 30 mmHg, which also leads to
indicates that patients at both extremes Based on the above-mentioned a decrease in ocular resistance.
of the blood pressure spectrum are discussion of the associations of OPP
at greater risk of glaucoma. This with glaucoma, it can be very well In the study done by Ramli et al.31, no
apparent paradox at the extremes can summarised that following may be the difference was found in the OPP between
be explained by two factors: (a) patients reasons for hypertensives to have an the patients with NTG and controls
with hypotension suffer from low OPP increased risk of open angle glaucoma: when it was measured during the day.
at the ONH and (b) patients of chronic However, they found that OPP measured
hypertension develop atherosclerosis A. Reduction in OPP below critical at night showed a significant difference
later in life, causing an increased level of auto regulation between the groups, being lower in
NTG patients. Sung et al32 compared
B. Structural changes in arterioles due progressing and non-progressing NTG
to hypertension
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Subspeciality-Glaucoma
patients and found that the progressing Drugs altering OPP in ocular blood flow. In a placebo
group had wider 24-h fluctuations in controlled double blind study46,
mean arterial pressure and mean OPP. 1. Carbonic anhydrase inhibitors treatment with ginkgo has also induced
Choi et al.33 reported that instability of (CAI) some reversibility of visual field damage
24-hour MOPP is one of the major risk They shorten the arteriovenous transit in normal tension glaucoma.
factors for the development of NTG time. CAI accelerate the macular and
and is often found in association with optic nerve head capillary dye transit The Cerebrovascular System
greater degree of visual field changes at as well as increase the ocular pulse in Glaucoma
the initial presentation itself. Charlson amplitude and the pulsatile ocular Glaucoma is also considered as a
et al.34 stated that patients with blood flow, both in glaucoma patients neurodegenerative disorder of the
DOPP < 35 mmHg have a 2.3-fold higher and in normal subjects40. World central visual system. Reports have
probability of progression of NTG when Glaucoma Association Consensus stated that at the point where the optic
compared to the patients with DOPP in recognized that CAI have been shown to nerve axons end ie. the lateral geniculate
the higher quartile. Thus, day and night improve ocular blood flow beyond their nucleus, there is atrophy present due
differences, or fluctuations in OPP may hypotensive and perfusion pressure to oxidative damage, in the patients of
be more important in the development effects41. Acetazolamide has also been glaucoma47. The watershed area of the
or progression of NTG. However, in the reported to increase choroidal and brain consists of optic tracts, the lateral
study conducted by Quaranta et al.35 retinal blood flow, possibly increasing geniculate nuclei, the optic radiations,
there was no significant association oxygenation of ocular tissues, thus and the visual cortex.
found between 24-h MOPP and VF improving the OPP42. Recently, clinical These zones are more prone to
damage in Caucasian NTG patients. studies with up to 6 months follow- hypoperfusion and ischemia under the
up have been published on blood situations of unstable perfusions like
Scientific evidence supporting flow changes induced by topical CAIs low BP etc. It is due to these ischemic
applied in the usual clinical dosage insults that the visual system becomes
the role of OPP in glaucoma all the more gullible to the neural
2. Prostaglandin F2-alpha analogs degeneration48.
Dysfunction of the systemic vascular Certain studies43 show that
endothelium is known to occur in prostaglandin F2-alpha analogs OPP in clinical practice
patients with NTG, with associated (travoprost, latanoprost, and Ideally, OPP should be measured in
defects in the release of certain bimatoprost) increase the ocular blood every suspect of glaucoma as it is a
endothelium-derived vasodilators. A flow and thus OPP. noninvasive, inexpensive, and easy to
high percentage of NTG patients obtain procedure. It not only gives the
(45%) have documented episodic The table 4 shows the effect of information regarding the glaucoma
myocardial ischemia36. There is also various anti-glaucoma drugs on IOP risk of the patient but also helps us with
a significant correlation between management44. a brief overview of patient’s systemic
slower cerebrovascular blood flow 3. Ginkgo biloba extract health. If cost and time constraints are
and decreased central visual function It has been shown to increase the OPP. not there, one may implement the OPP
indices (eg, visual field mean defect Chung et al.45 evaluated a possible assessment as a part of glaucoma work-
value, logMAR visual acuity) in patients therapeutic effect of Ginkgo biloba up.
with OAG37. Choroidal blood flow extract (GBE) on glaucoma patients
provides marginal oxygen delivery who may benefit from improvements
to photo receptors in dark adapted
situations and thus low OPP can Table4: Effect of various anti-glaucoma drugs on IOP management and OPP
damage the photo receptors. Levels of
Endothelin 1, a potent vasoconstrictor Class Average IOP Nocturnal Efficacy OPP
have been elevated in OAG patients. Reduction
Evidence propose that the death of
retinal ganglion cells is mediated by Prostaglandin 18–31% during day More effective than Increases
effects of ET-1 independent of, or in analogs time and about 8% beta blockers with IOP
addition to, ischemia, including the during night time in reductions of about
possibilities of astrocyte proliferation supine position 8.5–17%
and effects from changes in endothelin
B receptor expression38. In the Canadian Beta-blockers 20–27% during day Little or no effect No effect
Glaucoma Study, visual field loss time
progression was seen more in the
patients with vasospasm.39 Alpha-agonists 12.5–29% Little or no effect No effect
Carbonic anhydrase 13.2–22% Modest efficacy Increases
inhibitors
92 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
Measurement of OPP is useful in the the arterial pressure at the entrance to it will simply segregate the effect of
POAG patients with IOP in the normal the eye and the venous pressure at the the IOP or BP term. Ideally, dynamic
range (Table 5). exit of the eye. However, no methods visualisation of the blood flow in the
The Collaborative Normal-Tension are available at present for such direct vessels supplying the optic nerve head
Glaucoma Study49 recognised the measurements. Hence, OPP is measures should be done. Brachial blood pressure
optic disc hemorrhage as well as as a difference between the arterial is unlikely to reflect true perfusion
migraine as the predictive factors for pressure which is measured in the arm pressure at the optic nerve head.
progression, and the Low-Pressure and the IOP. However, these values Moreover, the diurnal variation in the
Glaucoma Treatment Study (LoGTS)50 may not represent the actual measures. measurements of blood pressure and
identified decreased mean OPP and According the current equation used, a IOP is not taken into account during
the use of systemic antihypertensive decrease in BP or increase in the IOP may the calculation of OPP by the simple
medication as risk factors for visual result into the fall in OPP. The irony is equation.
field progression. that these parameters cannot be tested
Assessment of OPP might also benefit separately to assess the relationship How to modify OPP?
patients with optic disc hemorrhage. with glaucoma as they all appear in the
In LoGTS, low mean OPP as well as same equation. It is important to properly review the
low mean SBP, migraine headache, and medical history of the patient. If a
use of systemic beta-blockers were all A single measurement of BP and IOP patient is on anti-hypertensives, which
associated with the development of gives a brief insight to the OPP. But, since significantly decreases the nocturnal
optic disc hemorrhage51. both vary widely, a single calculation diastolic pressure, shifting of the
Patients with progressive glaucoma cannot complete characterization medications from the bed time towards
despite having an adequately low IOP of OPP. If a low OPP is the cause for evening should be considered. This is
level should also be considered for OPP glaucoma progression, a proper diurnal because taking these anti-hypertensives
assessment. Charlson et al. concluded assessment will be required. A 24-hour during bed time may cause significant
that reduction in mean arterial pressure ambulatory BP monitoring will help drop in the nocturnal mean arterial
from daytime to night time was a in revealing the “nocturnal dippers” pressure.
significant predictor of visual field whose BP drops down at night.
progression in such patients34. If a patient has stable glaucoma with
Patients with a history of low BP, or on Is OPP really required in low OPP, one may advice to further
multiple systemic antihypertensive modification of glaucoma lower the IOP by 1 to 3 mm Hg. If the
medications, or who having history treatment? glaucoma is unstable, then one may
of orthostatic hypotension should Various population-based studies monitor 24- hour blood pressure and
undergo OPP measurement. have documented the role of ocular recommend salt loading if nocturnal
Table 5 : Patient subgroups in perfusion pressure in the development OPP is reduced. Salty snacks and fluid
which OPP measurement should and progression of OAG. Basic scientific volume at bedtime may also be tried
be considered studies have outlined the importance to keep BP from dropping out during
Normal-tension glaucoma of oxidative stress in the course of OAG sleep, mainly in the patients whose
progression. Vascular risk factors have anti-hypertensive medications cannot
Eyes with optic disc haemorrhage also been reported to influence the be altered or decreased.
Patients with progression at low IOP status of open-angle glaucoma. All these
History of low BP, multiple systemic factors, pave the way towards involving Topical beta-blockers have been
antihypertensives, symptoms of the OPP, as a modifiable risk factor in found to lower the BP at night in some
orthostasis the management of glaucoma. patients53. There switching over to
Patients with nocturnal hypotension another class of anti-glaucoma drugs
However, after adjustment for baseline may be considered in these patients.
How to characterise OPP? IOP, the Rotterdam Study7 has found no
Ideally the IOP should be calculated significant relation between OPP and Punctal occlusion after administration
by the difference estimated between incident OAG. The Beijing Eye study8 of anti-glaucoma drug should be
has also not found any significant recommended to decrease the amount
relation between the two. Moreover, the of systemic absorption of the eyedrops,
study conducted in Great Britain52stated which will help to overcome the blood
that taking into consideration only OPP pressure–lowering effect of those drugs.
is not an appropriate surrogate for the
true optic nerve perfusion, because Conclusion
if we adjust either the BP or the IOP,
The concept of OPP takes into account,
both the BP and IOP. However, we still
www.dosonline.org/dos-times DOS Times - Volume 26, Number 4, January-February 2021 93
Subspeciality-Glaucoma
don’t know which of the two factors 10. Sommer A, Tielsch JM, Katz J, et al. 20. Kim KE, Oh S, Baek SU, Ahn SJ, Park KH,
play a superior role in manipulating the Relationship between intraocular Jeoung JW. Ocular Perfusion Pressure
OPP. Moreover, we till date do not have pressure and primary open angle and the Risk of Open-Angle Glaucoma:
sufficient evidence to prove the fact that glaucoma among white and black Systematic Review and Meta-analysis.
increasing the BP will actually help in Americans. The Baltimore Eye Survey. Sci Rep. 2020 Jun 22;10(1):10056.
retarding the progression of glaucoma. Arch Ophthalmol. 1991; 109(8):1090-
If we incorporate this concept of OPP 1095. 21. Mitchell P, Lee AJ, Rochtchina E, Wang
in our daily practice, this would require JJ. Open-angle glaucoma and systemic
changing the existing concept of the 11. Bonomi L, Marchini G, Marraffa M, hypertension: the Blue Mountains Eye
target IOP algorithm too. Hence, this Bernardi P, Morbio R, Varotto A. Vascular Study. J Glaucoma 2004; 13: 319–326.
concept of OPP seems to be interesting risk factors for primary open angle
as a modifiable risk factor of glaucoma. glaucoma: the Egna- Neumarkt Study. 22. Asrani S, Zeimer R, Wilensky J, Gieser D,
Ophthalmology. 2000;107(7):1287-1293. Vitale S, Lindenmuth K. Large diurnal
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Subspeciality-Glaucoma
Clinical Trials in Glaucoma
Talvir Sidhu1, Nikhil Agrawal2
1. Assistant Professor of Ophthalmology, GMC Patiala.
2. Assistant Professor of Ophthalmology, AIIMS Bathinda.
Introduction OHTS I evaluated the role of topical females were excluded from the study.
Glaucoma is the leading cause of ocular hypotensive medications in Participants were randomly assigned
irreversible blindness in the world prevention or delaying the development to treatment group or observation
with 60.5million affected in the world. of primary open angle glaucoma group. Ocular hypotensive medication
Management of glaucoma (medical (POAG). were given to achieve IOP reduction
or surgical) requires evidence based of ≥20% from baseline to achieve
approach to identify the methods of OHTS II: This study evaluated whether target IOP of <24mmHg. Diagnosis of
treatment-approach which best suits a delay in treatment of patients with glaucoma on follow-up was made on
the stage of glaucomatous disease in ocular hypertension exacts a penalty. basis of development of a reproducible
patients. Multiple large scale clinical visual field defect or change in optic
trials have shown light upon the Objectives nerve head. The primary outcome was
medical and surgical treatment in development of a reproducible visual
glaucoma. This paper discusses an OHTS I: This study had two major field defect or optic nerve head change
overview of major clinical trials in objectives. The primary objective of the due to development of POAG.1
glaucoma. study was to establish whether topical In OHTS II, the treatment group of
ocular hypotensive medication result OHTS I participants continued the use
The following trials have been covered in prevention or delay of development of medications and the observation
in this review: of POAG in patients with ocular group was started on treatment after 7.5
hypertension. The secondary objective years of start of treatment.2
1. Ocular Hypertension Treatment was to assess the risk factors leading Results
Study (OHTS) I & II to development of a visual field defect OHTS I: The study recruited 1636
or optic nerve head change in ocular individuals, of whom 817 received
2. Early Manifest Glaucoma Trial hypertensives. ocular hypotensive medications and
(EMGT) 819 were assed to observation. The
OHTS II: To determine the effect of baseline IOP in medication group was
3. Collaborative Normal Tension delayed treatment in OHT by assessing 24.9±2.6mmHg and in observation
Glaucoma Study (CNTGS) the cumulative proportion of POAG group was 24.9±2.7mmhg. The mean
development in treatment group versus reduction of IOP in medication group
4. Collaborative Initial Glaucoma observation group. was 22.5±9.9%. At 5 years of follow-up,
Treatment Study (CIGTS) 4.4% of medications group and 9.5% of
Methodology observation group developed POAG.3
5. Advanced Glaucoma Therefore, reduction of IOP in ocular
Intervention Study (AGIS) OHTS I study aimed to recruit minimum hypertensives reduced the chances of
of 1500 subjects of 40-80 years age, who developing POAG by half. According to
6. The tube versus trabeculectomy had ocular hypertension, with IOP of secondary objective, the persons who
study (TVT study) one eye between 24-32mmHg and other developed glaucoma had higher age,
eye 21-32mmHg. Both eyes had to meet higher baseline IOP, thinner central
7. Ahmed vs Baerveldt study (AVB) the eligibility criterion of IOP, had open corneal thickness, greater pattern
angles, >2 normal visual fields and visual standard deviation and increased cup-
8. Laser in Glaucoma and ocular acuity > 20/40. Atleast 25% of patients disc ratio.4 African-american origin
HyperTension study (LiGHT) recruited were of African-american participants had a higher chance of
Ocular Hypertension Treatment origin. Participants with previous developing glaucoma.
Study (OHTS) I & II intraocular surgery, secondary IOP
elevation, narrow angles on gonioscopy,
Ocular Hypertension CD ratio difference of >0.2, diabetic
Treatment Study (OHTS) I & II retinopathy and pregnant or nursing
The OHTS is a multicentric trial done
in 22 clinical centers in United States of
America.
96 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
OHTS II: at 13 years of followup (7.5 Objectives treat analysis, where if IOP exceeded
years of OHTS I & 5.5 years of OHTS 25mmHg in treated eyes or 35mmHg in
II), the cumulative proportion of POAG The primary objective of EMGT was to control eyes, latanoprost 50ug/ml was
in observation group was 0.22 versus compare the effect of lowering IOP by added.5 3 monthly followup visits were
0.16 in treatment group.2 The median immediate start of therapy versus late done to confirm visual field progression,
time to develop glaucoma was lesser or no treatment, on the progression of repeat photographs and confirm IOP
in observation group than treatment newly diagnosed POAG, measured by elevation.
group. The individuals at higher risk visual field defects or optic disc changes.
of developing glaucoma at baseline Outcomes
(CCT<555um; IOP>25.75mmHg; CD The secondary objectives were to
Ratio>0.5)4 had higher cumulative determine the extent of IOP reduction Perimetric endpoint: Significant
proportions developing glaucoma in by treatment protocol, to describe the progression of the same 3 or more points
observation group. natural history in glaucoma, and to in pattern deviation change probability
explore factors leading to progression maps in 3 consecutive C30-2 Humphrey
Limitations in glaucoma. fields.
The study had stringent and narrow Methodology Optic disc endpoints: Comparison of
criterion for POAG diagnosis, especially baseline and follow-up photographs by
with exclusion of diabetic retinopathy. Newly diagnosed and untreated flicker chronoscopy with confirmation
The IOP reduction under 24mmHg glaucoma (N=255), 50-80 years of by side-by-side grading in 3 follow-up
or 20% may be insufficient for some age were recruited from a large-scale photographs.
patients especially with multiple risk population-based screening of 44,243
factors. The incidence of POAG cannot residents of Malmo and Helsingborg Results
be estimated from this study as it is not (194/255) or patients followed from
a population based study. screening (22/255) or referred from The mean age of the participants was
eye specialists (22/255) or patients 68.1 years, 66% being females. One
Conclusions already following at clinical centers fifth had a family history of glaucoma.
(17/255). The diagnosis of glaucoma GHT outside normal limits was found
Overall, OHTS I & II concluded that was made on basis of repeatable visual in 97% of participants at baseline,
treatment in ocular hypertension field defects in one or both eyes. The 9 patients developed abnormal
prevents and delays the development diagnosed cases consisted of chronic fields on follow-up; median mean
of POAG. It also determined specific open angle glaucoma, normal tension deviation -4.1dB.5 The average IOP was
risk factors that can used to categorize glaucoma and exfoliation glaucoma. 20.6mmHg (13-30.5mmHg) with 80%
ocular hypertensives into high risk Visual fields were documented in of eyes having baseline IOP<25mmHg.
group. Also, the high risk group have Humphrey 24-2full threshold fields Exfoliation glaucoma occurred in
higher proportions developing POAG and analyzed by Statpac II. Persons 10% of patients. 126 patients received
if treatment is delayed. Therefore, high with GHT outside normal limits on treatment and 126 did not receive
risk OHT should be monitored carefully 2 consecutive fields or Borderline treatment initially.
and closely, and early treatment may be affecting the same GHT sector with
beneficial in these cases. localized glaucomatous changes was At 6 years of followup, IOP reduction
taken as a visual field defect. Advanced of 25% was seen throughout followup.
Early Manifest Glaucoma Trial visual field defects with MD<-16 dB Higher baseline IOPs had higher IOP
(EMGT) or a threat to fixation were excluded. reduction on treatment; 0.6mmHg
Other exclusion criterion were visual more reduction for 1mmHg higher
Early Manifest Glaucoma trial is the acuity <0.5, mean IOP >30mmHg or baseline IOP. IOP reduction was
first largest randomized clinical trial any IOP>35mmHg in atleast one eye, decreased by cardiovascular disease.6
to evaluate and compare the role of any condition precluding visual field IOP remained stable in most patients
IOP reduction in progression of treated or optic disc photographs. If both eyes except exfoliation glaucoma showed
versus untreated early glaucoma in had visual field defects, one eye should larger change of IOP per year (median
patients with normal to moderate have MD better than -10 dB and other of 0.98mmHg/year). Progression was
IOP elevations at diagnosis. It allowed eye MD better than -16dB. The patients seen less in treatment group (45%)
us to elucidate the natural history of were randomized into treatment or as compared to controls (68%) and
newly diagnosed glaucoma without control group. The treatment group was occurred late in treatment group.
treatment. It also evaluated the factors given betaxolol eye drops 0.5% twice The median rates of visual function
leading to progression in glaucoma. daily and argon laser trabeculoplasty. loss were maximum in exfoliation
The trial was done with intention to glaucoma than NTG/POAG.7 Overall
progression is seen in 68% of control
www.dosonline.org/dos-times DOS Times - Volume 26, Number 4, January-February 2021 97
Subspeciality-Glaucoma
patients; 74% of POAG with median IOP reduction: 25% IOP reduction was inhibitors were used only when eye
time of 44.8 months, 56% of NTG in seen throughout followup. More IOP to be randomized in study had been
median time of 61.1 months and 93% of reduction was seen with higher baseline decided. In patients undergoing
exfoliation glaucoma in median time of IOPs, with minimal reduction in filtering surgery, 20% IOP reduction
19.5 months. baseline IOP<15mmhg. Cardiovascular was accepted and no more than 3
disease presence decreased IOP surgical procedures were allowed in
EMGT treatment halved the risk of reduction effect of treatment. one eye. Regular, three monthly follow-
progression with 10% decreased risk up visits were done to assess the eyes
with each mmHg IOP decrease from Factors influencing glaucoma progression: under treatment. Progression was
baseline.8 Baseline factors that increased higher mean IOP during follow, considered to be confirmed when four
progression were higher followup irrespective of baseline IOP, thin CCT, of five consecutive follow-up fields
IOP, older age, pseudoexfoliation, lower systolic BP in lower baseline showed progression relative to baseline
bilateral disease, lower mean deviation IOP and cardiovascular disease in fields, with at least one nonperipheral
and disc hemorrhages at follow-up.9 higher baseline IOP were risk factors progressing point (or the one central
At long-term followup, other factors for progression. These risk factors may point) being common to all four fields.
that emerged to increase progression demand lower target follow-up IOPs to
were lower ocular perfusion pressure, further reduce progression in addition Results
cardiovascular disease in high baseline to management of systemic risk factors.
IOP, lower systolic BP in patients Out of 230 enrolled patients, only 145
with low baseline IOP, thinner CCT Natural history of glaucoma: in patients (5 patients withdrew) eyes could ne
in patients with high baseline IOP.10 with early or moderate glaucoma with randomized: 79/140 in control group
Mean IOP was a significant risk factor moderately elevated IOP, progression and 61/140 in treatment group. 35%
for progression, with hazard ratio of is seen in 68% of patients; with faster of control eye and 12% of treated eyes
11% for every 1mmHg rise of IOP, and higher progression in exfoliation showed progression in 1695±143 days
irrespective of IOP fluctuations.11 glaucoma cases. and 2688±123 days respectively. 14%
Presence of disc haemorrhages in developed cataracts in control group
glaucoma were 55% in all patients, Collaborative Normal Tension and 38% in treated group, mainly
did not differ in treatment or control Glaucoma Study (CNTGS) attributable to filtration surgery.15 An
group and were associated with time to overall survival analysis showed a
progression.12 Glaucoma progression in Objectives survival of 80% in the treated arm and
manifest glaucoma could be detected of 60% in the control arm at 3 years,
using visual field loss first in 52% eyes The objectives of the study were to assess and 80% in the treated arm and 40% in
and optic disc first in 12% eyes.13 Also whether normal tension glaucoma was the controls at 5 years.16 Patients who
visual fields could detect progression an IOP dependent disease and does start benefitted most from treatment had
more often in all stages of manifest of treatment halt progression in NTG. no disc hemorrhage at baseline, female
glaucoma cases.14 gender, family history of glaucoma, no
Methodology history of cardiovascular disease and no
Conclusions family history of stroke. IOP lowering
Normal tension glaucoma was was also effective in patients with
EMGT is a large randomized trial, defined as median IOP of <20mmHg migraine.17 Risk factors for progression
which selected patients of early to in 10 measurements with visual field were migraine, disc hemorrhage,
moderate glaucoma with moderately abnormality and optic disc changes. and female gender. Family history of
elevated to normal IOP. A fixed protocol 230 patients of 20-90 years age were glaucoma or untreated IOP levels did
of treatment was chosen, which lead enrolled from 24 collaborating centers. not affect the progression.18
to a mean 25% reduction in IOP from Patients using systemic beta blockers
baseline. or clonidine were excluded. After Limitations
enrollment, randomization was done
According to primary objective, to receive treatment or not, after noting The central corneal thickness was not
treatment group was associated with evidence of progression using visual measured and visual fields criteria were
lower and delayed progression with field or progressive optic disc cupping changed over course of study. Use of
50% reduced risk of progression in or disc hemorrhage. Treatment was disc hemorrhage as a sign of progression
treatment group, with 10% decreased aimed adducing the IOP by 30% within was used for randomization at the
risk for each mmHg IOP decrease from 6 months. Beta-adrenergic blockers or entrance of study but not as end point.
baseline. alpha-agonists were not used in any Cataract formation was very frequent
eye due to potential cardiovascular in the study leading to affected visual
According to secondary objectives: side effects. Carbonic anhydrase
98 DOS Times - Volume 26, Number 4, January-February 2021 www.dosonline.org/dos-times
Subspeciality-Glaucoma
field assessment, which was used as end adaptation were the most frequently sequences of surgical treatment with
point for progression. reported symptoms related to visual Argon laser trabeculoplasty (ALT)
function, whereas visual distortion was and trabeculectomy (Trab) in case
Conclusions the most bothersome. Increased visual of medically uncontrolled advanced
field loss was significantly associated glaucoma. To clarify the clinical course
IOP reduction of 30% slows the with higher dysfunction among five of treatment in advanced glaucoma
progression in NTG. Faster progression disease-specific QOL measures.20 after surgical intervention.
occurs on females, history of migraine, At 8 year followup, > 3 dB of MD from
and disc hemorrhages. The effect of baseline was found in 21.3% and Methodology
cataract formation had to be corrected 25.5% of the initial surgery and initial
to elucidate the beneficial effect of IP medicine groups. The mean IOP ranged Randomized, multi-centre trial enrolled
lowering in NTG. from 17.1-18.3 mmHg in the medicine eyes with advanced open angle
group, or 13.8- 14.4 mmHg in the glaucoma not managed on maximum
Collaborative Initial surgery group. IOP always under 18 was tolerated medicine, from 11 clinical
Glaucoma Treatment Study 8% at nine years in medicine group, centers between 1988 and 1992. 591
(CIGTS) and 51% at nine years in the surgery patients (789 eyes) were randomly
group.21 Medicine group showed assigned to one of two sequences of
Objectives significant associations of MD over time surgical treatments. One sequence
with all three IOP summary measures started with argon laser trabeculoplasty
To compare the outcomes of initial – the maximum IOP (p=0.0003), the (ALT) followed by trabeculectomy
treatment with medications or by range of IOP (p<0.0001), and the SD and by a second trabeculectomy if
immediate filtration surgery for newly of IOP (p=0.0056), but not in surgical the first trabeculectomy failed (ATT
diagnosed open-angle glaucoma. group. Initial surgery lead to less VF sequence). The other sequence started
progression in advanced cases, whereas with trabeculectomy, is followed by
Methodology diabetics experienced more VF loss after ALT if the trabeculectomy failed, and
surgery.22 Early post-op complications by a second trabeculectomy should ALT
607 newly diagnosed POAG/ pigmentary were reported in 50% patients, shallow failed (TAT sequence). Follow-up time
glaucoma/ pseudoexfoliative glaucoma anterior chamber in 13%, encapsulated ranged between 4 and 10 years. The
were enrolled into the study with IOP bleb in 12%, ptosis in 12%, serous CD primary outcome was visual acuity.25
>20mmHg and established visual field in 11% and hyphema in 10%.23 Long Severity of glaucomatous visual field
defect or IOP>27 with glaucomatous term cataract extraction was performed defects was analyzed with the 24-2
disc change and normal visual field. A in 20% post trabeculectomy. 14% threshold program in Humphrey VF
best-corrected ETDRS visual acuity score required bleb revision atleast once. The Analyzer.
of 70 or greater in each eye; and an age risk of blebitis and hypotony at 5 years
between 25 and 75 years. In the surgical were 1.5% and endophthalmitis was Results
arm, the patient’s study eye underwent 1.1%.24
trabeculectomy within 14 days of Conclusions 451 eyes belonged to 332 black patients,
randomization and in the medical Range of IOP, SD of IOP and maximum 325 eyes of 249 white patients and 13
arm, patients received a sequence of IOP play an important role in visual field eyes of 10 other races were studied.
medications that usually began with a progressioninmedicallytreatedpatients Blacks were younger, with more severe
topical beta blocker. Primary outcome of POAG. Therefore, IOP fluctuations visual field losses, more hyperopic and
variables were visual field progression in patients should be carefully noted had more systemic co-morbidity of
and Quality of Life. Secondary outcome and more aggressive IOP control may diabetes and hypertension.26 Followup
variables were visual acuity, IOP and be required in these patents. Initial ranged from 4-10 years.
cataract formation. 19 surgery has its own complications,
although IOP fluctuations are less in IOP and visual field predictive analysis
Results post trabeculectomy patients. showed that patients with a mean
IOP <14 mmHg in the first 18 months
607 patients entered the study with Advanced Glaucoma had minimal mean change in visual
307 randomized to medical group and Intervention Study(AGIS) fields, as opposed to patients with IOP
300 for surgery group. The baseline Objective between 14 and 17 mmHg and those
demographics were similar in both. 38% To compare the outcome of two with IOP over 17 mmHg, both of whom
of study participants were blacks. 90.6% had progression. Also, eyes which had
had POAG; 4.8% had pseudoexfoliation all visits IOP of less than 18 mmHg
and 4.6% had pigmentary forms of over the course of follow-up (mean
open-angle glaucoma. Difficulty with IOP 12 mmHg) had no deterioration
bright lights and with light and dark
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Subspeciality-Glaucoma
of the mean visual field defect score.27 were enrolled. Patients who had had IOP<14mmHg. A significantly
Whereas, patients with IOP<18mmHg no light perception or active iris greater use of medications was seen
in less than 50% of visits showed neovascularization or ICE syndrome or in tube group in first 2 years, was
progression. aphakia or uveitis were excluded. Study thereafter similar in both groups. Tube
Within ATT sequence, the blacks had patients were randomized to undergo group had 25% complete success while
lower probability of failure than TAT. placement of a 350mm2 Baerveldt trabeculectomy had 29% complete
Black patients needed more medications glaucoma implant or trabeculectomy successes. The cumulative probability
than whites in both sequences.28 The with mitomycin C (0.4 mg/ml for 4 of failure was 29.8% in the tube group
failure of ALT/surgery was associated minutes).32 Failure was defined as and 46.9% in the trabeculectomy group
with pre-intervention, younger age, IOP>21mmHg or no reduction below at 5 years. The overall incidence of
high IOP, diabetes mellitus and post- 20% from the baseline at 3 months late postoperative complications was
operative complications.29 The risk or IOP<5mmHg after 3 months, similar in both groups.36
factors for sustained vision loss and reoperation needed for glaucoma,
visual field loss were less baseline visual or loss of light perception. Serious Conclusion:
field defect, male gender, worse baseline complications were defined as loss
visual acuity.30 The expected 5-year of 2 or more lines of Snellen’s visual Both procedures were associated
cumulative probability of cataract acuity or re-operation to manage the with similar IOP reduction and use
formation after trabeculectomy complication. of supplemental medical therapy at
increased to 78%, associated with 5 years. Additional glaucoma surgery
post-operative inflammation and flat Results was needed more frequently after
anterior chamber.31 trabeculectomy with MMC than tube
Limitations 212 eyes of 212 patients were shunt placement.
Optic disc assessment was done enrolled; 107 in tube group and 105 in
using slit lamp biomicroscopy, not trabeculectomy group. The baseline IOP Ahmed vs Baerveldt study
stereoscopic photographs. There was was 25.3 ± 5.3mmHg on mean 3.1 ± 1.2 (AVB)
low interobserver agreement among glaucoma medications. 81% had POAG,
ophthalmologists. 44% had undergone cataract surgery, Objective:
Conclusions 35% had undergone trabeculectomy
It was found that lowering IOP to less and 20% combined surgery. The To compare the outcomes in refractory
than 14 with minimal fluctuations, intraoperative complications occurred glaucoma patients undergoing
reduces progression in advanced in 7% in tube group and 10% in placement of Ahmed versus Baerveldt
glaucoma. Black patients fair worse trabeculectomy group.33 Post-operative glaucoma drainage implants.
with initial trabeculectomy. The risk complications developed in 34% in
factors for failure of surgery is younger tube group and 57% in trabeculectomy Methodology
patients and a high baseline IOP. group. Surgical complications
associated with reoperation and/ Patients aged 18-85 years, with
The tube versus or loss of ≥2 lines visual acuity were glaucoma refractory to medical and
trabeculectomy study (TVT similar in both groups. Early post-op surgical treatment were included in an
study) complications, most common was international randomized multicentric
Objectives choroidal effusion and shallow AC, study conducted at 16 sites. POAG
To compare the safety and efficacy of which were similar in both groups. with failed trabeculectomy or
trabeculectomy to tube shunt surgery in Wound leak and hyphema were more secondary glaucoma without previous
eyes with previous intraocular surgery. in trabeculectomy group. surgery, who have higher failure risk
Methodology of trabeculectomy were included.
A total of 212 patients were enrolled At 1 year, IOP was 12.4±3.9 mmHg in the Patients with previous cyclodestructive
in a multicenter randomized clinical tube group and 12.7±5.8 mm Hg in the procedure or aqueous shunt or scleral
trial conducted at 17 clinical centers trabeculectomy group. The probability buckling or presence of silicone oil or
from 1999 to 2004. Glaucoma patients of failure was 4% in tube group and vitreous in the anterior chamber were
having uncontrolled IOP 18-40mmHg, 13.5% in trabeculectomy group. excluded. Patients were randomized to
More trabeculectomy failures were receive either an Ahmed valve glaucoma
counted due to persistent hypotony.34 drainage implant (124 patients) or
At 5 years, IOP was similar in both a Baerveldt (non-valved) glaucoma
groups (p=0.12).35 IOP reduction from drainage implant (114 patients).
baseline of 41% was seen in tube group
and 49.5% in trabeculectomy group. The primary outcome measure was
Approx 63% patients in both groups failure, defined by any of the following
criteria: 1. IOP > 21 mm Hg or not
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