volume 31 No 2 14-12-2020

DJO Vol. 31, No. 2, October-December 2020

Photo essay

Granular Corneal Dystrophy Type II

Siddharth Madan, Sarita Beri

Department of Ophthalmology, Lady Hardinge Medical College and Associated S.S.K.H & K.S.C. Hospital, University of Delhi, India.
.

A paradigm shift has been observed in the classification of Granular corneal dystrophies (GCD). GCD is a bilateral,
progressive, genetically determined and non-inflammatory disease limited to the cornea that has an autosomal
dominant mode of inheritance. A 28 year old young male presented to us without any visual complaints. The
examination of his cornea revealed the presence of diffuse linear, multiple round to granular, bread crumb like
Abstract and stellate opacities extending from the sub-epithelium migrating down till the deep stroma, the classical clinical
features of a heterozygous phenotypic variant of GCD type II.It progresses slowly and majority of the affected patients
maintain a stable vision. Since this patient was asymptomatic therefore a complete ophthalmic examination in
routine cases presenting to the oupatient clinics is indispensible. Various management options exist but a definitive
treatment option is lacking.

Delhi J Ophthalmol 2020;31;99-102; Doi http://dx.doi.org/10.7869/djo.605
Keywords:. Granular Corneal Dystrophy Type II, Corneal Dystrophy.

A paradigm shift has been observed in the classification of for applying for a driving license. He apparently had no visual
Granular corneal dystrophies (GCD) which can be attributed complaints. On examination his unaided visual acuity (VA) in
to the 2005 creation of The International Committee on the both eyes (BE) was 6/9. Bilateral cornea revealed the presence
Classification of Corneal Dystrophies (Table 1 and 2).1, 2, 3 of diffuse linear, multiple round to granular, bread crumb
GCD is a bilateral, progressive, genetically determined and like and stellate opacities extending from the sub-epithelium
non-inflammatory disease limited to the cornea that has an migrating down till the deep stroma (Figure 1 and 2). There
autosomal dominant mode of inheritance. Transforming was no significant refractive error on cycloplegic refraction,
growth factor beta-induced (TGFβI) gene located on intraocular pressure was 12 and 14 mm Hg in the right
chromosome 5q31 codes for keratoepithelin, a type of eye and left eye respectively Bilateral fundus examination
corneal stromal protein secreted by corneal epithelium. was unremarkable and so was the ocular examination in
Recent research has suggested that excessive accumulation all other aspects. Although immunohistochemical testing
of the C-terminal of the mutant TGFB-I p (TGFB-I protein) to demonstrate a positive reaction with antibodies to
as a result of mutation in this gene results in crystalloid microfibrillary protein, immunoglobulin G in the kappa and
accumulation in GCD corneas which plays a principal role lambda light chains and light microscopy to stain hyaline
in the pathobiology of GCD.4 5 A 28 year old male tailor by and amyloid deposits with Masson trichome/Congo red
occupation presented to us for his ophthalmic examination was not performed nor was any genetic testing done on the
patient, yet the clinical appearance was highly suggestive
of a heterozygous phenotypic variant of GCD type II. GCD
type II mostly starts in the second decade of life, visual acuity
is rarely worse than 6/24 and these patients infrequently
demonstrate recurrent corneal erosion (RCE) symptoms.
The corneal opacities in heterozygous patient progress
slow and majority maintain a stable VA.6 Significant visual
disabilities occur only later due to the natural history of

Figure 1: A-D: Slit lamp examination of the cornea of the right eye (Figure.1A) Figure 2: A-B: Rings or stellate-shaped snowflake stromal opacities between
and the left eye (Figure.1C) reveal the presence of diffuse linear, multiple the superficial stroma and the mid stroma along-with lattice lines in deeper
round to granular, bread crumb like and stellate opacities extending from the cornea are seen in the right eye on indirect retroillumination (2A) and also in
sub-epithelium migrating down till the deep stroma. Torch light examination
of the right eye (Figure.1B) and the left eye (Figure.1D) show multiple dot like the left eye (2B).

corneal opacities.

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DJO Vol. 31, No. 2, October-December 2020

Table 1: Descriptive categories developed by IC3D committee the disease. Therefore our patient was instructed for a
reexamination six months later and was educated on the
Category Description possibility of development of RCE symptoms. GCD type II
C1 is observed globally now with a prevalence of 11.5 affected
Gene has been mapped and persons per 10,000 population as per a Korean study
C2 identified and specific mutations and the term Avellino addressing this dystrophy is now
are known. obsolete. Broadly, GCD usually requires no treatment.1
C3 Pressure patching, bandage contact lenses, artificial tear and
C4 Dystrophy mapped to 1 or hyperosmotic sodium chloride drops are first line options
more specific chromosomal loci, in RCE cases. Topical treatment in the form of steroids,
but the gene(s) remains to be immunomodulators, autologous serum and topical and oral
identified. macrolides are second line agents. Surgical intervention is the
final treatment option that aims to reduce the frequency of
The disorder has not yet been RCE symptoms and improve VA. Anterior stromal puncture
mapped to a chromosomal locus. and phototherapeutic keratectomy provides a less invasive
alternative to penetrating keratoplasty (PK) in GCD patients
A suspected new, or previously
documented, corneal dystrophy,
although the evidence
supporting it being distinct, is
not yet convincing.

Table 2: The IC3D classification and specific assays for various dystrophies

Type of dystrophy Category Specific assays

Epithelial and Subepithelial Dystrophies some C1 Maps (Sheets of intraepithelial, multilamellar, basal laminar material on
Light microscopy {LM}).
1. Epithelial basement membrane dystrophy Dots – Cogan (Intraepithelial pseudocyst containing cytoplasmic debris on
LM).
(EBMD)—majority degenerative Fingerprint lines (Rib-like intraepithelial extensions of basal laminar material
on LM).
2. Epithelial recurrent erosion dystrophy C4; C3 Bleb (Irregular, subepithelial accumulation of fibrillogranular material on
(ERED) C4, (Smolandiensis variant) C3 LM).

2. Epithelial recurrent erosion dystrophy C4; C3 Franceschetti corneal dystrophy (FRCD) - Alcian blue– positive deposits.
(ERED) C4, (Smolandiensis variant) C3 Partial destruction and absence of the Bowman layer with intervening
avascular connective tissue, pannus between the basal epithelium and
3. Subepithelial mucinous corneal dystrophy C4 Bowman layer. Negative Congo red staining.
(SMCD) Keloid-like structure stains positive with Congo red indicating secondary
4. Mutation in keratin genes: Meesmann C1 amyloidosis in C3.
corneal dystrophy (MECD)
Franceschetti corneal dystrophy (FRCD) - Alcian blue– positive deposits.
5. Lisch epithelial corneal dystrophy (LECD) C2 Partial destruction and absence of the Bowman layer with intervening
avascular connective tissue, pannus between the basal epithelium and
6. Gelatinous drop-like corneal dystrophy C1 Bowman layer. Negative Congo red staining.
(GDLD) Keloid-like structure stains positive with Congo red indicating secondary
amyloidosis in C3.
Bowman Layer Dystrophies C1
Subepithelial band of eosinophilic, periodic acid–Schiff–positive, Alcian blue–
1. Reis–Bücklers corneal dystrophy positive, hyaluronidase-sensitive material is present anterior to Bowman
layer.

Intraepithelial cysts are seen filled with periodic acid–Schiff–positive cellular
debris. The epithelium may be thickened and disorganized. Thickened
multilaminar basement membrane with projections into the basal epithelium
is observed.
Stocker–Holt Variant
The cornea in its entirety demonstrates fine, grayish punctate epithelial
opacities that stain with fluorescein and fine linear opacities that may appear
in a whorl pattern

Diffuse cytoplasmic vacuolization of all cells in the affected area is seen. There
is scattered staining on Ki67 immunohistochemistry

Subepithelial and stromal amyloid deposits are observed.

Bowman membrane is replaced by a sheet-like connective tissue layer with
granular deposits that stain red with Masson trichrome.

(RBCD)—Granular corneal dystrophy type 3

2. Thiel–Behnke corneal dystrophy (TBCD) C2 Irregular thickening of the epithelial layer forming ridges and furrows of
C1, potential variant underlying stroma, with focal absences of epithelial basement membrane.
Bowman layer is replaced by a fibrocellular layer between epithelium and
stroma with a pathognomonic wavy saw-toothed pattern.

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3. Grayson –Wilbrandt corneal dystrophy C4 Characterized by variable patterns of opacification in the Bowman layer of
(GWCD) the cornea which extend anteriorly into the epithelium with decreased to
normal visual acuity.

Stromal Dystrophies C1 Epithelial atrophy and disruption with degeneration of basal epithelial
1. TGFBI corneal dystrophies C1 cells is seen with focal thinning or there is absence of Bowman layer that
A. Lattice corneal dystrophy progressively increases with age.
a. Lattice corneal dystrophy, TGFBI type Eosinophilic layer is observed between epithelial basement membrane and
(LCD): Classic lattice corneal dystrophy (LCD1), Bowman layer; and stromal deposition of amyloid substance distorts the
variants (III, IIIA, I/IIIA, and IV) are C1 architecture of corneal lamellae.
b. Lattice corneal dystrophy, gelsolin type
(LCD2) (This is not a true corneal dystrophy but is
included here for ease of differential diagnosis)

B. Granular corneal dystrophy C1 C1 GCD type 1- Multiple stromal deposits extend from deep epithelium to
Descemet membrane.
i. Granular corneal dystrophy, type 1
GCD type 2- Deposition of both typical deposits as observed in GCD1 along-
(classic) (GCD1) with deposition of amyloid is seen on LM. Individual opacities stain with
either Masson trichrome or Congo red.
ii. Granular corneal dystrophy, type 2 C1
GCD type 3- There is an absence of the Bowman layer and a band of abnormal
(granular-lattice) (GCD2) connective tissue is seen between the corneal epithelium and stroma but
without the characteristic fuchsinophilic bodies.
iii. Granular corneal dystrophy, type 3 C1

(RBCD) = Reis–Bücklers

2. Macular corneal dystrophy (MCD) C1 Glycosaminoglycans (GAGs) accumulate intracellularly and extracellularly
in the corneal stroma, corneal endothelium, and Descemet membrane (stain
positively with Hale colloidal iron or Alcian blue).
There are 3 variants of macular corneal dystrophy, based on the
immunoreactivity of the macular deposits specific for the sulfated epitopes
on antigenic keratan sulfate (AgKS):
1. Type I: No AgKS reactivity in the cornea or in the serum.
2. Type IA: Keratocytes manifest AgKS reactivity but the extracellular
material does not. Serum lacks AgKS.
3. Type II: All the abnormal accumulations react positively with
AgKS and the serum has normal or lower levels of AgKS.

3. Schnyder corneal dystrophy (SCD) C1 Abnormal deposition of intra- and extracellular esterified and phospholipids
and cholesterol is observed in basal epithelial cells

4. Congenital stromal corneal dystrophy C1 The stromal lamellae are separated from each other in a regular manner.
(CSCD)

5. Fleck corneal dystrophy (FCD) C1 Swollen and vacuolated keratocytes are seen which contain GAG and
complex lipids.

6. Posterior amorphous corneal dystrophy C3 Irregular stromal architecture is observed anterior to a thin Descemet
(PACD) membrane and focal attenuation of endothelial cells.

7. Central cloudy dystrophy of François C4 Faint undulating appearance of the deep stroma and positive staining for
(CCDF) GAGs is characteristic

8. Pre-Descemet corneal dystrophy (PDCD) C4 Enlarged keratocytes are seen in the posterior stroma with vacuoles and
intracytoplasmic inclusions containing lipid-like material

Descemet Membrane and Endothelial Dystrophies C1, C2, or Diffuse thickening and lamination of Descemet membrane is seen. Sparse

1. Fuchs endothelial corneal dystrophy C3 and atrophic endothelial cells, hyaline excrescences on thickened Descemet

(FECD) membrane called guttae is typical

2. Posterior polymorphous corneal C1 or C2 Descemet membrane with multiple layers of collagen on its posterior surface
dystrophy (PPCD) hereditary endothelial C2 manifesting focal fusiform or nodular excrescences.

3. Congenital To date there is no convincing published evidence to support the existence of
dystrophy 1 (CHED1) autosomal dominant (AD) CHED as a distinct entity and hence AD CHED,
formerly known as CHED1 has been removed from the classification system.
4. Congenital hereditary endothelial C1
dystrophy 2 (CHED2) – Autosomal recessive, now Diffuse thickening and lamination of Descemet membrane. Sparse and
called CHED atrophic endothelial cells.

5. X-linked endothelial corneal dystrophy C2 Moon crater endothelial changes and subepithelial band keratopathy.
(XECD) Epithelium and Bowman lamella thinning. Anterior stroma with irregularly
arranged collagen lamellae.Descemet membrane thickening with small
excavations and pits. Loss of endothelial cells or atypical appearance.

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to control RCE symptoms. Femtosecond Deep anterior Cite This Article as: Siddharth Madan, Sarita Beri. Granular
lamellar keratoplasty (FDALK) and femtosecond laser- Corneal Dystrophy type II. Delhi Journal Of Ophthalmology.2020;
assisted keratoplasty (FLAK) enhance treatment outcomes. Vol 31, (2) 99-102
Acknowledgments: Nil
References Conflict of interest: None declared
Source of Funding: None
1. Roncone DP. Granular corneal dystrophy: a novel approach to Date of Submission: 12 April 2020
classification and treatment. Optom Vis Sci. 2014 Mar; 91(3):e63- Date of Acceptance: 21 May 2020
71.
Address for correspondence
2. Weiss JS, Møller HU, Lisch W, Kinoshita S, Aldave AJ, Belin MW, Siddharth Madan, M.B.B.S, M.S, D.N.B
et al. The IC3D classification of the corneal dystrophies. Cornea.
2008 Dec;27 Suppl 2:S1-83. (Ophthalmology), F.I.C.O

3. Weiss JS, Møller HU, Aldave AJ, Seitz B, Bredrup C, Kivelä T, et Affiliation: Assistant Professor, Department
al. IC3D classification of corneal dystrophies--edition 2. Cornea. of Ophthalmology, Lady Hardinge Medical
2015 Feb;34(2):117–59. College and Associated S.S.K.H & K.S.C.
Hospital, University of Delhi, New Delhi
4. Folberg R, Alfonso E, Croxatto JO, Driezen NG, Panjwani N, Email : [email protected]
Laibson PR, et al. Clinically atypical granular corneal dystrophy
with pathologic features of lattice-like amyloid deposits. A study
of these families. Ophthalmology. 1988 Jan;95(1):46–51.

5. Lee EJ, Kim KJ, Kim HN, Bok J, Jung SC, Kim EK, et al. Genome-
wide scan of granular corneal dystrophy, type II: confirmation of
chromosome 5q31 and identification of new co-segregated loci
on chromosome 3q26.3. Exp Mol Med. 2011 Jul 30;43(7):393–400.

6. Han KE, Kim T, Chung WS, Choi S, Kim B, Kim EK. Clinical
findings and treatments of granular corneal dystrophy type
2 (Avellino corneal dystrophy): a review of the literature. Eye
Contact Lens. 2010 Sep; 36(5):296–9.

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Photo essay

Association of Goldenhar with Duane’s Retraction Syndrome

Shagun Korla, Savleen kaur, Jaspreet Sukhija

Advanced eye centre (Department of Ophthalmology) Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Abstract A six-year girl presented with history of deviation of eye and facial asymmetry. Diagnosis of Goldenhar syndrome (GHS)
with Duane retraction syndrome (DRS) was made. This case highlights DRS as an unusual but known association of
Goldenhar Syndrome. Patient with GHS presenting to an ophthalmologist should be screened for vertebral, cardiac,
renal and central nervous system defects.

Delhi J Ophthalmol 2020;31;103-104; Doi http://dx.doi.org/10.7869/djo.606
Keywords: Goldenhar Syndrome, Duane's Retraction Syndrome, Microsomia, Branchial Arch Syndrome

A six-year girl presented with history of deviation of eye and 40%, and ear anomalies in 40% of the cases.
facial asymmetry (A). On examination, there was a notch
in the upper lid (B) and preauricular skin tags (C). Ocular DRS is an unusual but known association of GHS. Incidence
motility showed (D) deficient adduction (black arrow) and of Duane Retraction Syndrome(DRS) with GHS is around
abduction (white arrow). Diagnosis of Goldenhar syndrome 5% in sporadic and 10% in familial cases. The frequent
(GHS) with Type III Exotropic Duane retraction syndrome association of DRS with other congenital anomalies might be
(DRS) was made. suggestive of teratogenic event occurring between the fourth
to eighth week of gestation as an etiological factor.6
GHS is known by various names depending upon the
components of the disease complex. This includes craniofacial Patient with GHS presenting to an ophthalmologist should
microsomia, oculo-auriculo-vertebral syndrome, hemifacial be screened for vertebral, cardiac, renal and central nervous
microsomia and Ist and IInd branchial arch syndrome. system defects
The pathognomic triad includes presence of epibulbar
dermolipoma or bulbar dermoid, low set ears and vertebral References
skeletal anomalies.1,2
1. Harley: Paediatric Ophthalmology, Vol II, Saunders Company.
GHS affects derivatives of the first and second brachial arch.3 1983 (1041-1043.1243)¬
Abnormalities are unilateral in 85% and bilateral in 10–33%
of the cases and the right side is more frequently affected.4 2. Feingold, M, and Gabis. S: Ocular abnormality associated with
Ophthalmic features include microphthalmia,dermoids, 1st and lied arch syndrome: Survey Ophthal. 14:30, 1968.
coloboma, cataract and strabismus.Ocular anomalies mainly
bilateral dermoids are seen in 60%, vertebral anomalies in 3. Verma MJ, Faridi MM. Ocular motility disturbances (Duane
retraction syndrome and double elevator palsy) with congenital
heart disease, a rare association with Goldenhar syndrome--a
case report. Indian J Ophthalmol. 1992;40:61-2.

4. Bielicka B, Necka A, Andrych M. Interdisciplinary treatment of

Figure 1: Composite photograph of a 6-year girl highlighting the association of Goldenhar and Duane’s Retraction Syndrome. A: She presented with a facial
asymmetry and low set ears. B: There was a notch in the upper lid and preauricular tags (C). Ocular motility revealed deficient adduction and abduction (D).

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patients with Goldenhar Syndrome – Clinical reports. Dent Med
Probl. 2006;43:458–62.
5. Kulkarni V, Shah M, Parikh A. Goldenhar syndrome: A case
report. J Postgrad Med. 1985;31:177–9.
6. Patrick A, Anthony R, Rudolph S, Suqin G. Duane's retraction
syndrome. Survey of Ophthalmology. 1993;38: 257-88.

Cite This Article as: Korla S, Kaur S, Sukhija J. Association
of Goldenhar with Duane’s Retraction Syndrome Delhi Journal
Of Ophthalmology.2020; Vol 31,No 2, Page 103-104

Acknowledgments: Nil

Conflict of interest: None declared

Source of Funding: None

Date of Submission: 29 April 2020
Date of Acceptance: 11 May 2020

Address for correspondence
Savleen Kaur Assistant Professor

Advanced Eye Centre
PGIMER, Chandigarh
Email: [email protected]

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DJO Vol. 31, No. 2, October-December 2020

Abstract PG Snippet

Deviant Behaviour in Third nerve Palsy

Savleen Kaur, Shagun Korla, Jaspreet Sukhija

Post Graduate Institute of Medical Education and Research, Chandigarh, India

29-year male presented with the complaints of diplopia for 4 years following a road traffic accident 5 years
ago and drooping of left eye. A diagnosis of aberrant regeneration of third nerve was made. MRI revealed
temporal lobe contusion. Aberrant regeneration may be a sign of underlying cavernous sinus tumour or
aneurysm. Patient was stable at a follow up of 8 months and was advised surgery.

Delhi J Ophthalmol 2020;31;105-106; Doi http://dx.doi.org/10.7869/djo.607
Keywords: Third nerve paralysis, aberrant regeneration, oculomotor palsy.

29-year male presented with the complaints of diplopia References
for 4 years following a road traffic accident and drooping
of left eye. On examination best corrected visual acuity was 1. Sibony PA, Lessell S, Gittinger JW Jr: Acquired oculomotor
20/20 OU with left mild ptosis and an exotropia of 25 prism synkinesis. Surv Ophthalmol 28:382–390, 1984.
diopters in primary gaze. There was limitation of elevation,
depression and adduction of the left eye(figure). Marked 2. WeberED,NewmanSA.Aberrantregenerationoftheoculomotor
lid retraction was observed on looking down (pseudo-Von nerve: implicationsforneurosurgeons. Neurosurg Focus. 2007;
Graefe’s phenomenon, white arrow)and adduction (lid-gaze 23:E14.
dyskinesis,black arrow).
A diagnosis of aberrant regeneration of third nerve was 3. Schatz NJ, Savino PJ, Corbett JJ: Primary aberrant oculomotor
made. MRI revealed temporal lobe contusion. Aberrant regeneration. A sign of intracavernous meningioma. Arch
regeneration should be kept in mind as a possible late Neurol 34:29–32, 1977
manifestation of recovering third nerve palsy.1,2 It may be a
sign of underlying cavernous sinus tumour or aneurysm.3,4 4. Slavin, ML, Einberg KR: Abduction defect associated with
Surgery on horizontal muscles of the non-involved eye aberrant regeneration of the oculomotor nerve after intracranial
improves the eyelid position.5 Patient was stable at a follow aneurysm. Am J Ophthal 121:580–582, 1996
up of 8 months and was advised surgery.
5. O'Donnell FE, Del Monte M, Guyton DL. Simultaneous correction
of blepharoptosis and exotropia in aberrant regeneration of the
oculomotor nerve by strabismus surgery: a new, simplified
ptosis correction for selected cases. Ophthalmic Surg. 1980
Oct;11(10):695-7.

Figures 1: 29-year male highlighting limitation of elevation, depression and adduction of the left eye with mild ptosis. Marked lid retraction on looking down
(white arrow) and adduction (black arrow).

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DJO Vol. 31, No. 2, October-December 2020

Cite This Article as: Kaur S, Korla S, Sukhija J.Deviant
Behaviour in Third nerve Palsy Delhi J Ophthalmology. 2020;31
(2):105-106
Acknowledgments: Nil
Conflict of interest: None declared
Source of Funding: None
Date of Submission: 04 May 2020
Date of Acceptance: 11 May 2020

Address for correspondence
Jaspreet Sukhija Additional Professor

Advanced Eye Centre
Post Graduate Institute of Medical
Education and Research, Chandigarh, India.
E mail: [email protected]

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DJO Vol. 31, No. 2, October-December 2020

PG Snippet

Complete Fleischer’s Ring

Kshama Popat
Cornea and Anterior Segment Consultant, Thakorbhai V. Patel Eye Institute (TVPEI), Shri M. L. Vaduwala Eye Hospital, Vadodara, India.

Abstract Fleischer’s Ring is a hemosiderin or iron ring seen at the base of cone in moderate to advanced cases of keratoconus. It
occurs due to deposition of iron from tear film. It is best visualized on cobalt blue filter which is highlighted here along with
the slit lamp biomicroscopy image.

Delhi J Ophthalmol 2020;31;107; Doi http://dx.doi.org/10.7869/djo.608

Keywords: Keratoconus, Fleischer’s ring.

Fleischer’s ring

Fleischer’s Ring is a hemosiderin or iron ring seen at the
base of cone in moderate to advanced cases of keratoconus.1
It occurs due to deposition of iron from tear film. Iron
gets deposited in the form of hemosiderin in the basal
epithelial cells at the level of base of the cone. Duration at
which, Fleischer’s ring appears is variable – it can be seen in
subclinical or forme fruste cases also, but in general, it occurs
in keratoconus at mild-moderate stage. It is best visualized
on cobalt blue filter as seen in (Figure 1a). Slit image of same
is seen in (Figure 1b). Surgical significance being it should be
entirely included in trephining while doing keratoplasty for
keratoconus to prevent recurrence in the graft.2

References

1. Romero-Jimenez M, Santodomingo-Rubido J, Wolffsohn JS.
Keratoconus: a review. Cont Lens Anterior Eye. 2010; 33(4): 157-66.

2. De Toledo JA, de la Paz MF, Barraquer RI, Barraquer J. Long-term
progression of astigmatism after penetrating keratoplasty for
keratoconus: evidence of late recurrence. Cornea. 2003;22(4):317 23

Cite This Article as: Kshama Popat. Complete Fleischer's Ring.
Delhi J Ophthalmology. 2020;31 (2): 101

Acknowledgments: Nil

Conflict of interest: None declared

Source of Funding: None

Date of Submission: 08 April 2020
Date of Acceptance: 15th June 2020

Address for correspondence

Kshama Popat FMRF(Cornea),

MS(Ophthalmology)

Cornea and Anterior Segment Consultant,
Thakorbhai V. Patel Eye Institute (TVPEI),
Shri M. L. Vaduwala Eye Hospital,
Vadodara, India.
Email : [email protected]

Figures 1: Complete Fleischer's Ring as seen with cobalt blue filter on slit lamp
in Fig 1a and same on slit lamp image in Figure 1b

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DJO Vol. 31, No. 2, October-December 2020

PG Snippet

Radiological Features of Thyroid Eye Disease (TED)

Ayushi Agarwal, Samreen Khanam, Akash Raut, Ruchi Goel

Department of Ophthalmology Guru Nanak Eye Center, Maulana Azad Medical College, New Delhi, India

Abstract This article highlights the importance of imaging and its current utility in Thyroid Eye Disease
(TED). Assessment of various disease parameters, surgical planning, characterization
of severity and activity, identification of sight-threatening disease and differentiation
from other orbital inflammatory disorders, makes imaging an indispensable tool in TED.

Delhi J Ophthalmol 2020;31;108-110; Doi http://dx.doi.org/10.7869/djo.609

Keywords: Thyroid Eye Disease, Imaging, Grave’s Orbitopathy.

Introduction proptosis using mid-axial orbital CT scan was first described
by Hilal and Trokel in 1977.1A straight line is drawn between
Thyroid Eye Disease (TED) is a chronic inflammatory the anterior margins of zygomatic processes, using the mid-
disorder affecting the orbit and the periorbita. Although axial orbital scan. The distance between the anterior aspect of
imaging is not a mandatory criterion for diagnosing TED, it cornea and the inter-zygomatic line is then measured. Values
is a vital tool to assess abnormalities in clinically challenging > 21 mm or an asymmetry greater than 2 mm between the
cases. It not only aids in early detection but is also helpful in globes, is highly suggestive of proptosis. Another technique
assessing the response to treatment. Radiological evaluation of assessing proptosis is by measuring the distance between
in TED plays a major role in identification of optic nerve the inter-zygomatic line and posterior sclera. Less than
involvement, characterization of disease activity, surgical 1/3rd globe lying behind the inter-zygomatic line is strongly
planning prior to decompression and differentiating from indicative of proptosis. (Figure 1). It is worth noting that the
other causes of orbital inflammation and proptosis. Herein above two methods can be applied to both CT as well as MRI
we discuss the two most preferred imaging investigations in scan.
TED, Computed Tomography (CT) and Magnetic Resonance
Imaging (MRI). “Coca-Cola” sign2 – It refers to bilateral fusiform enlargement
of medial rectus muscle belly with sparing of tendinous
CT Scan insertions (unlike myositis, where tendinous involvement is
common), leading to bowing of the medial orbital wall, and
CT Scan is one of the most widely used imaging modalities in thus giving an impression of a Coca-Cola bottle. It is seen
TED owing to its ready availability and a shorter acquisition in chronic, long-standing cases of TED with characteristic
time. It also aids in surgical planning in TED as it offers medial wall remodeling resulting due to increased intra-
better visualization of osseous structures. orbital pressure. (Figure 2)

Measurement of proptosis– The technique for assessment of

Figure 1: Measurement of exophthalmos. CT scan, axial view, suggestive of Figure 2: Coca Cola Sign. A )Fusiform enlargement of bilateral medial rectus
right – sided exophthalmos muscle belly, with sparing of tendinous insertions. The enlarged muscle belly

results in bowing of the medial orbital wall, B) also known as the
Coca-Cola sign.

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CT scan is the imaging modality of choice for surgical fat suppressed sequences, helps in delineating fatty
planning- It provides an excellent visualization of the degeneration. Fat suppressed sequences enable the
bony orbit, fat, paranasal sinuses and extra-ocular muscles differentiation of the intense signal enhancement of EOMs,
(EOMs). This yields necessary information required prior to which would otherwise look as intense as fat. Interstitial
surgery. Pre- and post-operative volumetric CT studies have edema within the EOMs can be effectively demonstrated on
been utilized for the assessment of orbital decompression. Short T1 Inversion Recovery (STIR) sequence, T2 weighted
Recently, Navigation-assisted Three-dimensional (3D) imaging and TIRM (Turbo Inversion Recovery Magnitude)
reconstruction of CT for surgical planning of multiwalled sequence.
orbital decompression has become popular.3
Stripe Sign – It is best appreciated on Contrast-enhanced
MRI Scan T1-weighted fat-suppressed MRI scan. The extra-ocular
muscles have an outer orbital layer and an inner global
Preferred modality for assessment of activity – MRI signal layer (except levator palpebralis superioris). The inner
alterations of Extra-Ocular Muscles (EOMs) can detect active global, hypointense region expands progressively
TED. Signal Intensity Ratio (SIR) is defined as the ratio of the anterior to posterior and terminates prior to insertion on the
Signal Intensity (SI) of the most inflamed extra-ocular muscle globe, whereas the outer hyperintense region
and the adjacent temporalis muscle. Potential biomarkers (“stripe”, representing the orbital layer of the rectus
of active disease include higher Signal Intensity Ratios muscle) doesn’t expand to the same extent.4 (Figure 3)
(SIRs) on T2 and T1 with gadolinium (T1 Gad) sequences
and increased normalized-Apparent Diffusion Coefficient Orbital Apex: MRI is a more precise imaging modality than
(n-ADC) of the EOMs. Increased fat density, eyelid edema CT scan for visualization of optic nerve, orbital apex and soft
and enlarged lacrimal glands are the other findings seen in tissue details.
active disease.
Predictors of Dysthyroid Optic Neuropathy (DON)
Distinguishing acute phase from fibrotic phase. A on Imaging5,6
prolonged T2 relaxation time is seen in the presence of
edematous changes in EOMs owing to inflammation, • Enlarged Superior Ophthalmic Vein (SOV) diameter
suggestive of acute phase. This differentiation is specifically • Barrett’s Muscle Index – Every patient with a muscle
important for assessing response to treatment.
Assessment of EOMs- MRI is a more sensitive and specific index of > 60% must be screened for DON. The
tool for detecting EOM enlargement as compared to CT scan. sensitivity varies between 32% - 100%, the average being
Contrast-enhanced T1-weighted MRI combined with 67% (Figure 4)
• Intracranial herniation of orbital fat through Superior

Figure 3: Stripe sign. A) T1-weighted MRI (pre-contrast) B) T1-weighted fat-suppressed contrast-enhanced sequence showing inner hypointense region
surrounded by outer hyperintense area (“stripe”) in the right medial rectus muscle (orange arrow).

E-ISSN: 2454-2784  P-ISSN: 0972-0200 109 Delhi Journal of Ophthalmology

DJO Vol. 31, No. 2, October-December 2020

Orbital Fissure (94% sensitivity, 91% specificity) References
• Apical crowding (Figure 5) – Specific but less sensitive
1 Hilal SK, Trokel SL. Computerized tomography of the orbit using
indicator of DON thin sections. Semin Roentgenol. 1977;12:137-47.
• Enlarged lacrimal glands may be present.
• Increased Muscle Volume/Orbit Volume (MV/OV), a 2 Siakallis LC, Uddin JM, Miszkiel KA. Imaging Investigation
ofThyroid Eye Disease. Ophthalmic Plast Reconstr Surg. Jul/Aug
ratio of > 20% is suggestive of DON
• Positive correlation between severity of perineural fat 2018;34(4S Suppl 1):S41-S51.
effacement and DON has been observed. 3 Mahoney N, Grant MP, Susarla SM, Merbs S. ComputerAssisted

Three-Dimensional Planning for Orbital Decompression.
Craniomaxillofac Trauma Reconstr. 2015;8(3):211-217.
4 Lauer S, Silkiss RZ. "Stripe sign"- MRI characteristic of
extraocular muscles in tendon sparing thyroid eye disease. Orbit.

2020 Jun 22;1.
5 Birchall D,Goodall KL,Noble JL,Jackson A. Graves

ophthalmopathy: intracranial fat prolapse on CT images as an
indicator of optic nerve compression. Radiology. 1996

Jul;200(1):123-7.
6 Monteiro ML,Gonçalves AC,Silva CT,Moura JP,RibeiroCS,Gebrim

EM. Diagnostic ability of Barrett's index to detect dysthyroid optic
neuropathy using multidetector computed tomography. Clinics
(Sao Paulo, Brazil). 2008 Jun; 63(3):301-6.

Cite This Article as: Ayushi Agarwal, Samreen Khanam, Akash
Raut, Ruchi Goel. Radiological Features of Thyroid Eye Disease (TED)
Delhi Journal Of Ophthalmology.2020; Vol 31, (2) : 108-110

Acknowledgments: Nil

Conflict of interest: None declared

Source of Funding: None

Date of Submission: 17 Jul 2020
Date of Acceptance: 20 Jul 2020

Figure 4: Barrett’s Muscle Index. Vertical index is the percentage of orbital Address for correspondence
height occupied by vertical recti (1+3) along a line drawn through the optic Ayushi Agarwal Resident
nerve (6). Horizontal index is the percentage of orbital width occupied by the
Guru Nanak Eye Center,
horizontal recti (2+4) along a line drawn through the optic nerve (7). New Delhi, India
The greater of the two is the muscle index. Email : [email protected]

Figure 5: Apical crowding. Specific but less sensitive predictor of DON. Quick Response Code
www.djo.org.in
E-ISSN: 2454-2784  P-ISSN: 0972-0200 110

DJO Vol. 31, No. 2, October-December 2020

Letter to Editor

What example are we setting for younger generation during
COVID-19 pandemic: an emotional connect??

Rinky Agarwal, Nitin Gupta, Chanchal Gupta, Namrata Sharma

Department of Ophthalmology, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi,India.
.

Ongoing health crisis, the COVID-19 pandemic, infuriated by SARS CoV-2 virus has slayed many lives
in numerous nations. Psychological impact of this pandemic on health-care workers is profound
Abstract and inexpressible. We presently discuss its adverse effects on coming generation of health-care
professionals.

Delhi J Ophthalmol 2020;31;111-112; Doi http://dx.doi.org/10.7869/djo.610

Keywords: COVID-19; SARS CoV-2; clinicians

To the editor, any front-line worker. Increased expenditure on health
Ongoing health crisis infuriated by SARS CoV-2 virus has infrastructure and its effective utilization should be
slayed many lives in numerous nations.1 Psychological ensured by government and administration. The state
impact of this pandemic on health-care workers is profound should consider it as its responsibility to provide adequate
and inexpressible.2 equipment to corona warriors and financial security to their
A young and nascent mind gets more easily influenced by family in case of unfortunate human loss. It is also necessary
surroundings. In present era of technology, all germinating for all national and state medical organizations to stand in
brains who have not yet joined the doctor’s league are solidarity and connect more with the community or faith-
involuntarily exposed to a lot of unenthusiastic information. based establishments for building emotional attachment
In India, few corrupt national and local media channels with general public. Separate portals should be created
selfishly portray doctors in negative limelight for fame and and advertised to receive and solve queries from country’s
money. These passive information centres constantly blame budding clinicians. Motivational videos can also be released
doctors for country’s poor health care blatantly ignoring to upsurge hope, patience and self-activism among them
their commitment, perseverance and dedication. A brief during these tough and testing times. These brains should
interaction with the front-line workers serving in COVID-19 be nurtured to place humanity above everything else, albeit,
wards reveals the flipside of the profession. Long working without ignoring their own physical and mental health.
hours, excess patient inflow, altered sleep and eating habits, To conclude, evolving clinicians are like budding flowers
risk of infection, uncomfortable protective equipment, that require tender support from their seniors, government
physical fatigue, violence, false legal suites are few serious and public equally. The future may seem dark at present but
problems faced by these warriors at their workplace. At united, the dawn is not far.
personal level, forcible evacuation of their rental homes,
separation from families, loneliness, fear and worry are Reference
stressful.3 News regarding retracted health care for ill health-
care workers, untimely demise of young corona warriors and 1. World Health Organization. Coronavirus Disease (COVID‑2019)
inhuman denial of post-humous accommodations is adding Situation Reports. World Health Organization; 2020.
fuel to fire. Doctors not serving in the COVID-19 wards are Available from: https://www.who.int/emergencies/diseases/
witnessing low self-esteem, job losses, pay cuts, and decrease novel‑coronavirus‑2019/situationreports. 20 [Last accessed on 30
in new opportunities inclusive of clinical, academic and Jun 20].
research activities. Delayed medical entrance tests, shortage
of staff and limited clinical exposure is shattering confidence 2. Xiao, C., 2020. A novel approach of consultation on 2019 novel
of budding clinicians. All these negative influences may coronavirus (COVID-19)-related psychological and mental
refrain young brains from entering this hugely satisfying problems: structured letter therapy. Psychiatry Investig. 17 (2),
and noble profession. While this have minimal short-term 175–176.
effects, long-term outcomes may be adverse with the country
losing enthusiastic and devoted workforce. 3. Wong AH, Pacella-LaBarbara ML, Ray JM, Ranney ML, Chang
The government and the general public need to shield BP. Healing the Healer: Protecting Emergency Health Care
these upcoming active minds from malice and pessimism Workers' Mental Health During COVID-19 [published online
by providing all healthcare workers a more conducive ahead of print, 2020 May 3]. Ann Emerg Med. 2020;S0196-
environment. An urgent ban should be imposed on fake 0644(20)30336-X.doi:10.1016/j.annemergmed.2020.04.041
media trials released without proper verification and
enquiry. For security purposes, strict actions should be
invoked against people perpetuating violence against

E-ISSN: 2454-2784  P-ISSN: 0972-0200 111 Delhi Journal of Ophthalmology

DJO Vol. 31, No. 2, October-December 2020

Cite This Article as: Rinky Agarwal, Nitin Gupta, Chanchal
Gupta, Namrata Sharma. Delhi J Ophthalmology 2020; 31
(2):111-112.
Acknowledgments: Nil
Conflict of interest: None
Source of Funding: None
Date of Submission: 21 Jul 2020
Date of Acceptance 03 Aug 2020

Address for correspondence
Rinky Agarwal MD, DNB

Senior resident

Dr Rajendra prasad centre for ophthalmic
sciences, All India Institute of Medical
Sciences New Delhi, India.
E-mail- [email protected]

Quick Response Code

E-ISSN: 2454-2784  P-ISSN: 0972-0200 112 www.djo.org.in

DJO Vol. 31, No. 2, October-December 2020

Letter to Editor

“Comment on “Patterns of Ocular Trauma Presenting to the
Tertiary Eye Care Centre in the Islands of Andaman and Nicobar””

Bharat Gurnani1, Kirandeep Kaur2

1Department of Cornea and Refractive Services, Aravind eye hospital, Pondicherry, India.
2 Department of Pediatric Ophthalmology and Strabismus ,Aravind eye hospital, Pondicherry, India .

Delhi J Ophthalmol 2020;31;-113; Doi http://dx.doi.org/10.7869/djo.611

Dear Editor, References

We read the article “Patterns of Ocular Trauma Presenting 1. Das S, Rana M Patterns of Ocular Trauma Presenting to the Tertiary
to the Tertiary Eye Care Centre in the Islands of Andaman Eye Care Centre in the Islands of Andaman and Nicobar. DJO
and Nicobar” by Das et al1 with great interest. However, we 2020;30:20-26
have a few important questions and suggestions to make.
The important question in the methodology is that authors 2. Kuhn F, Morris R, Witherspoon CD, Mester V. The Birmingham
used what classification for classifying the traumatic injury Eye Trauma Terminology system (BETT). J Fr Ophtalmol.
Birmingham Eye Trauma Terminology System (BETTS)2 or 2004;27(2):206–10
the Ocular Trauma Score Classification system.3 The authors
have used ONTT guidelines for traumatic optic neuropathy 3. Yu Wai Man C, Steel D. Visual outcome after open globe injury:
with intravenous methyl-prednisolone 30mg bolus followed a comparison of two prognostic models--the Ocular Trauma
by 5.4 mg / kg/ body wt for 48 hour, but ONTT guideline Score andthe Classification and Regression Tree. Eye (Lond).
state that IV methylprednisolone 1 g was given (diluted in 2010;24(1):84-89
100 ml normal saline over 45 min) for 3 days. Then, oral
prednisolone 1 mg/kg in tapering dose is administered 4. Pirouzmand F. Epidemiological trends of traumatic optic nerve
for 2 weeks. Can the authors throw some light on this.4 injuries in the largest Canadian adult trauma center. J Craniofac
The authors have treated surgical aphakia with anterior Surg2012;23:516-20.
chamber IOL(ACIOL). At what duration postoperatively did
the ACIOL was implanted and did the authors encounter 5. Walters RF, McGill JI, Batterbury M, Williams JD. Complications of
any complications post operatively. At our centre, scleral anterior chamber lens implants and their effects on the endothelium.
fixated intraocular lens (SFIOL) is used considering the long
term complications of anterior chamber IOL like corneal Eye (Lond). 1989;3 ( Pt 6):690-695
decompensation and secondary glaucoma.5 The author have
highlighted in the methodology that those who had severe Cite This Article as: Bharat Gurnani, Kirandeep Kaur,
penetrating eye injury, globe rupture and had no vision (PL “Comment on“Patterns of Ocular Trauma Presenting to the Tertiary
negative) underwent enucleation under general anaesthesia. Eye Care Centre in the Islands of Andaman and Nicobar” ” Delhi J
Did any of these patients had endophthalmitis or pan Ophthalmology 2020; 31 (2):-113.
ophthalmitis and did the authors address penetrating eye
injury with primary repair? At our centre, the primary repair Acknowledgments: Nil
is addressed first and enucleation is performed only for pan
ophthalmitisafter informed consent. Conflict of interest: None

Source of Funding: None

Date of Submission: 02 Aug 2020
Date of Acceptance 31 Aug 2020

Address for correspondence

Bharat Gurnani, DNB

Aravind eye hospital,
Pondicherry, India,
[email protected]

E-ISSN: 2454-2784  P-ISSN: 0972-0200 113 Quick Response Code
Delhi Journal of Ophthalmology

DJO Vol. 31, No. 2, October-December 2020

Letter to Editor

Response to comment on Patterns of OcularTrauma Presenting to
the Tertiary Eye Care Centre in the Islands of Andaman and Nicobar

Sujit Das

Department of Department of Ophthalmology ANIIMS, Port Blair, India.

Delhi J Ophthalmol 2020;31;-114; Doi http://dx.doi.org/10.7869/djo.612

I would like to thank Gurnani B for his interest in the Cite This Article as: Sujit Das, “Response “Patterns of Ocular
article entitled “Patterns of Ocular Trauma Presenting to Trauma Presenting to the Tertiary Eye Care Centre in the Islands of
the Tertiary Eye Care Centre in the Islands of Andaman Andaman and Nicobar”” Delhi J Ophthalmology 2020; 31 (2):-114.
and Nicobar” In the article regarding treatment protocol I Acknowledgments: Nil
used ONTT reference with 24 hour duration, which actually Conflict of interest: None
was NASCISS II study protocol, with 48 hour duration. I Source of Funding: None
used Birmingham eye trauma terminology for eye trauma Date of Submission: 02 Aug 2020
classification and not a single case of endophthalmitis Date of Acceptance 31 Aug 2020
happened in this study. Anterior chamber intra ocular
lens (ACIOL) was put after 2-3 weeks. As we know that Address for correspondence
Scleral fixated IOL is the best option in case of aphakia in Sujit Das,
the modern erra, still I used ACIOL because there was no
scope for that. In the follow up period no complications were Department of Ophthalmology
noticed specially corneal decompensation and glaucoma. ANIIMS, Port Blair, India
Primary repair was done in all cases and enucleation was [email protected]
performed only after considering the fact that there is no
chance of vision recovery.

Quick Response Code

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DJO Vol. 31, No. 2, October-December 2020

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DJO Vol. 31, No. 2, October-December 2020

*AMD: age-related macular degeneration,
DME: diabetic macular edema,
CNVM: choroidal neovascularization secondary to pathologic myopia,
BRVO: ischemic branch retinal vein occlusion,
CRVO: central retinal vein occlusion

References:
1. CHRISTIAN PRÜNTE, NICOLE ETER Retina Today - March 2018

2. Novartis press release Jul 2019 Available at -https://www.novartis.com/news/media-releases/novartis-receives-positive-chmp-opinion-lucentis-treatment- preterm-
infants-retinopathy-prematurity-rop-disease-causing-visual-impairment-and-blindness (Assessed on 20 Sep 2019)

3. Accentrix® BSS effective from 29 Nov 18.

ACCENTRIX®
Presentation: Vial: Ranibizumab. Each vial contains 2.3 mg of ranibizumab in 0.23 mL solution. Pre-filled syringe: Ranibizumab. Each pre-filled syringe contains 1.65 mg of ranibizumab in 0.165 mL solution. Indications: •improvement and
maintenance of visual acuity and function and for reduction of vascular leakage and retinal oedema, in patients with neovascular age-related macular degeneration (AMD), •the treatment of visual impairment due to diabetic macular edema
(DME),•the treatment of macular edema following retinal vein occlusion (RVO)•the treatment of visual impairment due to choroidal neovascularization (CNV) secondary to pathologic myopia (PM). Dosage and administration: •The recommended
dose is 0.5 mg (0.05 mL) given as a single intravitreal injection. The interval between two doses injected into the same eye should not be shorter than 1 month. Wet AMD, DME, RVO, PM: •Treatment is initiated with one injection per month until
maximum visual acuity is achieved and/or there are no signs of disease activity. •Thereafter, monitoring and treatment intervals should be determined by the physician and should be based on disease activity as assessed by visual acuity and/or
anatomic parameters. •Monitoring for disease activity may include clinical examination, functional testing or imaging techniques (e.g. optical coherence tomography or fluorescein angiography). •While applying the treat-and-extend regimen, the
treatment interval should be extended by two weeks at a time for wet AMD and central RVO, or by one month at a time for DME and branch RVO. •Accentrix and laser photocoagulation in DME or in branch RVO: Accentrix has been used concomitantly
with laser photocoagulation in clinical studies. When given on the same day, Accentrix should be administered at least 30 minutes after laser photocoagulation. Accentrix can be administered in patients who have received previous laser
photocoagulation. •Accentrix must be administered by a qualified ophthalmologist using aseptic techniques. Broad-spectrum topical microbicide and anesthetic should be administered prior to the injection. •Not recommended in children and
adolescents. Contraindications: Hypersensitivity to ranibizumab or to any of the excipients, patients with active or suspected ocular or periocular infections, patients with active intraocular inflammation. Warnings and precautions: •Intravitreal
injections have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract. Therefore proper aseptic injection techniques must be used. Patients should be
monitored during the week following the injection to permit early treatment if an infection occurs. •Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of injection of Accentrix. Sustained IOP increases have also been
reported. Intraocular pressure and the perfusion of the optic nerve head must be monitored and managed appropriately. •There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors. A numerically higher
stroke rate was observed in patients treated with ranibizumab 0.5 mg compared to ranibizumab 0.3 mg or control; however, the differences were not statistically significant. Patients with known risk factors for stroke, including history of prior stroke
or transient ischemic attack should be carefully evaluated by their physicians as to whether Accentrix treatment is appropriate and the benefit outweighs the potential risk. •Available data do not suggest an increased risk of systemic adverse events
with bilateral treatment. •As with all therapeutic proteins, there is a potential for immunogenicity with Accentrix. •Accentrix has not been studied in patients with active systemic infections or in patients with concurrent eye conditions such as retinal
detachment or macular hole. •There is limited experience with treatment of patients with prior episodes of RVO and of patients with ischemic branch RVO (BRVO) and central RVO (CRVO). In patients with RVO presenting with clinical signs of
irreversible ischemic visual function loss, treatment is not recommended. •Should not be used during pregnancy unless the expected benefit outweighs the potential risk to the fetus. For women who wish to become pregnant and have been treated
with ranibizumab, it is recommended to wait at least 3 months after the last dose of ranibizumab before conceiving a child; use of effective contraception is recommended for women of child-bearing potential; breast-feeding is not recommended.
•Following treatment patients may develop transient visual disturbances that may interfere with their ability to drive or use machines. Patients should not drive or use machines as long as these symptoms persist. Interactions: No formal interaction
studies have been performed. Adverse drug reactions: •Very common (≥10%): intraocular inflammation, vitritis, vitreous detachment, retinal hemorrhage, visual disturbance, eye pain, vitreous floaters, conjunctival hemorrhage, eye irritation,
foreign body sensation in eyes, lacrimation increased, blepharitis, dry eye, ocular hyperemia, eye pruritus, intraocular pressure increased, nasopharyngitis, headache, arthralgia. •Common (1 to 10%): retinal degeneration, retinal disorder, retinal
detachment, retinal tear, detachment of the retinal pigment epithelium, retinal pigment epithelium tear, visual acuity reduced, vitreous hemorrhage, vitreous disorder, uveitis, iritis, iridocyclitis, cataract, cataract subcapsular, posterior capsule
opacification, punctuate keratitis, corneal abrasion, anterior chamber flare, vision blurred, injection site hemorrhage, eye hemorrhage, conjunctivitis, conjunctivitis allergic, eye discharge, photopsia, photophobia, ocular discomfort, eyelid edema,
eyelid pain, conjunctival hyperemia, stroke, influenza, urinary tract infection*, anemia, anxiety, cough, nausea, allergic reactions (rash, pruritus, urticaria, erythema). •Uncommon (0.1 to 1%) : blindness, endophthalmitis, hypopyon, hyphema,
keratopathy, iris adhesions, corneal deposits, corneal edema, corneal striae, injection site pain, injection site irritation, abnormal sensation in eye, eyelid irritation. •Serious adverse events related to intravitreal injections include endophthalmitis,
rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract.
*observed only in the DME population
Packs: Vial: Pack of 1 vial
Pre-filled syringe: Pack of 1 prefilled syringe

Before prescribing, please consult full prescribing information available from Novartis Healthcare Private Limited, Inspire BKC, Part of 601 & 701, Bandra Kurla Complex, Bandra (East), Mumbai – 400 051, Maharashtra, India. Tel +91 22
50243335/36, Fax +91 22 50243010

For the use of a registered medical practitioner or a hospital or a laboratory only.
India BSS dated 10 Oct 17 revised on 29 Nov 18 based on international BSS dtd 28 Oct 2014 effective from 29 Nov 18.

Novartis Healthcare Private Limited

Inspire BKC, Part of 601 & 701, Bandra Kurla Complex, Bandra (East), Mumbai – 400 051, Maharashtra, India
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