DOS Times_July-Aug19_04-02-2019_HR a

Subspeciality-Retina

ab behind the globe mimicking the optic
nerve. When the gain is decreased
c to suppress other scleral echoes, the
d choroidal mass is still readily apparent.
e
f Thus with the help of all above
Figure 2. (a) Fundus photograph: a round, irregularly elevated, orangish red lesion ~ 4 mentioned multimodal imaging
DD in macular area. Borders are well demarcated with an irregular geographic outline. techniques the diagnosis of choroidal
Irregular orange pigment clumps on the surface (orange arrow). Multiple short branching osteoma with sub-retinal fluid
vessels (blue arrow). NSD seen (green arrow). (b) FA: hyper- autoflourescent changes accumulation with no CNV was made.
around macula (yellow arrow). (c) SD-OCT: elevated area of neuro-sensory detachment These modalities also helped us to
(red arrow). (d) SS-OCT: dense hyperreflective dots spread into a hyporeflective matrix. differentiate choroidal osteoma from
Shadowing is seen (yellow arrow). Neuro-sensory detachment of retina (red arrow). (e) amelanotic choroidal melanoma/
FFA: early mid frame shows hyperflourescence in posterior pole around macula which nevus, choroidal metastases, choroidal
progresses till late frame. (f) ICGA : early central hypoflourescence at posterior pole around haemangioma, choroidal granuloma
macula. Mid frame shows stippled hyperflourescence in the lesion which increases till late etc.
frames.
There is no standard treatment for
choroidal osteomas. It has been seen
that tumor growth occurs in ~ 41-
64% of cases followed for a period of
10 years2. Most choroidal osteomas
have a slow random growth, on any
of the non-calcified margins, with an
increase in mean basal diameter of
around 0.37 mm per year. Trimble et al.
showed that tumor decalcification and
resolution occurs in around 50% cases
characterized by thin, atrophic, yellow-
grey region with overlying RPE and
choriocapillaris atrophy3. It’s associated
with poor long-term visual acuity when
the decalcification is located under the
fovea due to overlying photoreceptor
loss. Visual co-morbidity in choroidal
osteoma is usually due to subretinal
fluid accumulation, haemorrhages
or serous retinal detachment. Serous
retinal detachment occurs in choroidal
osteoma frequently in the absence of
CNV.

Treatment options for foveal choroidal
osteoma are limited. Observation is the
indicated management where there are
no symptoms, with fundus examination
at regular intervals monitoring for
signs of CNV. Song et al. have shown
cases where there have been complete
resolution of SRF with remission of
vision without any complications4.
Recent studies conducted show use
of ranimizumab and bevacizumab in
resolution of SRF5,6. Transpupillary
thermotherapy used in some cases
have also yielded positive results7.

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Subspeciality-Retina

Photodynamic therapy though used, is Ophthalmol. 2005 Dec; 123(12):1658-66. Choroidal Osteoma without Choroidal
mainly for the extra-foveal choroidal Neovascularization. J Ophthalmic Vis
osteomas8. 3. Trimble SN, Schatz H, Schneider Res. 2015 Oct-Dec; 10(4):484-6.
GB. Spontaneous decalcification of a 7. Yahia SB, Zaouali S, Attia S. Serous
To conclude, choroidal osteoma is a choroidal osteoma. Ophthalmology. retinal detachment secondary to
rare benign ossifying tumor mimicking 1988; 95:631-634. choroidal osteoma successfully treated
various malignant choroidal tumors. with transpupillary thermotherapy.
Hence, it is important to establish 4. Alameddine RM, Mansour AM, Kahtani Retinal Cases Brief Rep 2008; 2:126‑7.
a proper diagnosis with use of the E. Review of choroidal osteomas. Middle 8. Mazloumi M, Dalvin LA, Ancona-
various diagnostic modalities. The need East Afr J Ophthalmol. 2014 Jul-Sep; Lezama D, Mashayekhi A, Shields CL.
for active management may not be 21(3):244-50. Photodynamic therapy for extrafoveolar
required in cases similar to this. But we choroidal osteoma. Retina. 2019 Apr 2.
do recommend a close follow up of these 5. Mansour AM, Arevalo JF, Al Kahtani
patients to prevent any development of E, Zegarra H, Abboud E, Anand R, Corresponding Author:
complication. Ahmadieh H, Sisk RA, Mirza S, Tuncer
S, Navea Tejerina A, Mataix J, Ascaso Dr. Prathama Sarkar MS, DNB
References FJ, Pulido JS,Guthoff R, Goebel W, Roh Department Ophthalmology,
1. Gass JD, Guerry RK, Jack RL, Harris YJ, Banker AS, Gentile RC, Martinez IA, Deen Dayal Upadhyay Hospital, Hari Nagar,
Morris R, Panday N, Min PJ, Mercé E, New Delhi, India
G. Choroidal Osteoma. Arch Lai TY, Massoud V, Ghazi NG. Role of
Ophthalmol.1978 Mar; 96(3):428-35. Intravitreal Antivascular Endothelial
2. Shields CL, Sun H, Demirci H, Shields Growth Factor Injections for Choroidal
JA. Factors predictive of tumor growth, Neovascularization due to Choroidal
tumor decalcification, choroidal Osteoma. J Ophthalmol. 2014;
neovascularization, and visual outcome 2014:210458.
in 74 eyes with choroidal osteoma. Arch
6. Najafabadi FF, Hendimarjan SM,
Zarrin Y, Najafabadi MF. Intravitreal
Bevacizumab for Management of

50 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

Systemic Diseases

Ocular Manifestations in Turner’s
Syndrome

Shana Sood DNB, FICO, Sanjana Vatsa MS, Preethi Naveen MS
Cornea and Refractive Services, Dr. Agarwal’s Eye hospital, Chennai, India

26 yrs/F presented with low vision in Figure 1: Iris coloboma, microcornea. Figure 2: Iris coloboma, microcornea and
both eyes since 15 years. She was a cataract (OD) and cataract (OS).
known case of hypothyroidism and scan as absence of estrogen leads
early onset diabetes mellitus, patient to increased fragility of bones in women (45XO Monosomy). Incidence
was also undergoing hormonal therapy these patients1. Patient was already is known to be 1: 3000 (2000-5000)
for infertility. General examination undergoing hormonal replacement females at live birth2, but is much more
revealed short stature and obese built. therapy under a gynaecologists care common among pregnancies that do
Subjective refraction was (Table 1): elsewhere. Genetic counselling was not survive full term (miscarriages and
offered which explained to the patient still birth).
On examination patient had nystagmus regarding the high chances of infertility
in both eyes and exotropia in right associated with the disease, and the Types
eye. Slit Lamp examination revealed patient was made aware about the yy Classical Turner’s syndrome:
microcornea, typical iris coloboma and predominantly sporadic nature of the
subluxated lens with phacodonesis in syndrome (usually not transmitted to caused by complete absence of X
both eyes. Presenile cataract was seen the fetus). Rarely transmission of partial chromosome in all cells.
in left eye more advanced than right eye deletion of X chromosome to the fetus yy Mosaic Turner’s syndrome : caused
(Figure 1 and 2). has been reported, necessitating genetic by presence of XX in some cells and
evaluation of mother by karyotyping absence of X chromosome in some.
Dilated fundus examination showed and fetus by amniocentesis in antenatal This group of patients have slightly
retinochoroidal coloboma in both eyes period. better phenotypic appearance
(Figure 3 and 4). Intraocular pressure Discussion as compared to classical turner’s
(IOP) by applanation tonometry was Turner’s syndrome is a chromosomal syndrome patient .
16mm Hg in right eye and 26 mm Hg disorder caused by complete/partial Systemic Features3
in left eye. Patient underwent barrage absence of one X chromosome in yy Short stature, webbed neck, low
laser in both eyes to prevent retinal posterior hairline, broad chest
detachment. Antiglaucoma medication yy Cardiac Valve abnormalities
was started in the left eye to control IOP.
Cataract surgery was deferred to later
date.

Management
She was advised regular follow up with
medicine specialist for good control of
blood sugar and thyroid levels, she was
also recommended a bone densitometry

Table 1: Subjective Refraction

OD Sph Cyl Axis Vision OS Sph Cyl Axis Vision
100 6/60st Distance -0.00 -- -- PL+ve
Distance -6.00 -3.50 -- N24+ Near -- -- -- --

Near -- --

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Systemic Diseases

Figure 3 : Retinochoroidal coloboma (OD). Figure 4 : Retinochoroidal coloboma (OS).

yy Dysplastic kidney, Management of such patients need 29: 547-551.
yy Primary amenorrhea, infertility, multidisciplinary approach involving 3 M.Ibarra-Ramirez L.E. Martinez-de-
collaborative efforts of medical
streak ovaries specialist for blood sugar / thyroid Villareal. Clinical and genetic aspects
yy Thyroid dysfunction, diabetes levels, gynaecologist’s opinion for of Turner’s syndrome Medicina
hormone replacement therapy and Universitaria.2016;18(70):42-48.
mellitus (type II) regular bone densitometry evaluation to 4. Chrousos GA, Ross JL, Chrousos G, Chu
prevent stress fractures. Psychological FC, Kenigsberg D, Cutler G JR et al.
Ocular Manifestation4 support and genetic counselling is Ocular findings in Turner syndrome. A
yy Myopia, Colour Blindness of utmost importance to support the prospective study. Ophthalmology, 1984
yy Strabismus, Nystagmus patient’s treatment and keep the her Aug;91(8):926-8.
yy Microcornea, Corectopia, Iris well informed regarding the chances of
infertility. Corresponding Author:
Coloboma
yy Glaucoma, Premature cataract, References Dr. Shana Sood
1. Maria Felicia Faienza, Annamaria Cornea and Refractive Services,
subluxated lens Dr. Agarwal’s Eye hospital,
yy Chorioretinal coloboma Ventura, Silvia Colucci, Luciano Cavallo, Chennai, India
Myopia is usually managed with glasses. Maria Grano and Giacomina Brunetti.
Barrage laser is recommended in such Bone Fragility in Turner Syndrome:
patients to prevent retinal detachment Mechanisms and Prevention Strategies .
caused by breaks in intercalary 2016; 7: 34.
membrane. Strabismus can be corrected 2. C Gicquel, S Cabrol, H Schneid, F Girard,
by prismatic addition to glasses / surgery Y Le Bouc Molecular diagnosis of
and cataract surgery can be performed if Turner’s syndrome. J. Med. Genet.1992;
it is visually significant.

52 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

Monthly Meeting Update

Review of Advances in Improving
Accuracy in IOL Power
Calculations

J.S. Bhalla MS, DNB, MNAMS, Rakesh Verma DOMS
Deen Dayal Upadhyay Hospital, Hari Nagar, New Delhi, India.

Cataract surgery is the most common published by Fyodorov and Kolonko material of optic) affect ELP.
ophthalmological procedure performed in 1967 and was based on schematic
worldwide and has seen an exponential eyes. Numerous IOL power calculation yy Historical/refraction based.
growth in the past decade. The goal of formulae are available. They are either yy Regression analysis based: SRK, SRK-
cataract surgery is not only the removal mathematical (based on theoretical
of cataract, but also providing the patient optics), empirical (based on statistical II.
sharp, clear vision without glasses. regression analysis of a large number of yy Vergence formulae (based on
Despite all technological advancements implant patients) or a combination of
like femtosecond laser-assisted cataract the theoretical-empirical approaches. Gaussian optics).
surgery, Zepto capsulotomy, multifocal With advancement there has been Dr Holladay explained that the more
IOLs and toric IOLs, the improved increase in the complexity of IOL power you know about the anatomy of the eye
outcomes are dependent on precise calculation formulae. For many years, and the patient, the better you’ll be able
and accurate biometry. With modern most of the formulae including the to predict the effective lens position,”so
surgical techniques, the complications Holladay I, SRK/T, and Hoffer Q required as the no of variables increases, accuracy
have reduced significantly; however, only AL and K reading. Thomas Olsen of formulas also increases. Here we are
increasing emphasis is being laid then came up with a formula which classifying the formulas according to
on accurate refractive outcome to required four parameters: AL, K, ACD, their variables.
give spectacle independence to the and LT. In 1992 Holladay II formula,
patients. Newer biometry instruments which required seven variables for IOL 1. Two variable
that perform ocular measurements power calculation came into existence. yy Holladay 1
with micron precision and newer IOL Later Barrett suggested the Barrett yy SRK-T
calculation formulae to provide precise Universal II formula which yy Hoffer Q
IOL power required for intraocular required AL, K, ACD, LT and few 2. Three variable
lens implantation, therefore, form the optional variables. yy Haigis
backbone of refractive cataract surgery. The popular newer generation yy Ladas Super Formula
formulae include the Holladay 2, 3. Four variables
History of IOL power calculation Barrett Universal II, and the Hill- yy Olsen
formulas RBF. The common factor in all these 4. Five variable
The refractive power of the human eye formulae (except the Hill-RBF) is the yy Barrett Universal II
depends on the power of the cornea, need to predict effective lens position 5. Seven variable
the lens, the axial length (AL) of the or ELP.ELP is defined as distance from yy Holladay 2
eye and the axial position of the lens. the cornea to the principal plane of 6. Artificial Intelligence based
Calculation of accurate IOL power IOL. Both anatomical factors (K value, yy Hill-RBF
is an important step in the modern AL, Limbal WTW, Preop ACD, and LT) yy Clarke neural network
cataract surgery with successful IOL and IOL-related factors (shape, length,
implantation. flexibility, anterior angulation if any,
material of the haptic, and shape and
The first IOL power formula was

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Monthly Meeting Update

IOL power calculation Ray tracing: a modern approach
formulae Ray tracing is a method for calculating
the path of a single ray of light through
Theoretical Regression Modern a given optical system. As a ray passes
through an optical system, starting at
FYO DO ROV Original Modified Holladay I & II a given point and angle relative to the
Colenbrander SRK Hoffer SRT/T system’s optical axis, it is refracted at
Van DER HEUDE Hoffer Q each optical surface, causing the ray to
Binkhorst Shammas Haigis change direction.
SRK II
T2 When applied to IOL formulas, as in
Hoffer H-5 the Okulix software (Tedics Peric and
Ladas Super Formula JöherGbR; available at okulix.de), ray
Olsen tracing uses a pseudophakic eye model,
Barrett True K and ideally anterior and posterior
Barrett Universal II corneal surfaces should be measured
Hill RBF Calculator using topography. Okulix ray tracing
has a software interface to all Tomey
Figure 1. Classification of IOL formulas. devices, to the Pentacam (Oculus
Optikgeräte GmbH), and to the Lenstar
5. Ray tracing eyes, and post-radial keratotomy (Haag- Streit), thus allowing the user a
(RK) eyes. Intraoperative wavefront simple solution to use it with data from
yy Okulix aberrometry can also aid surgeons in these devices.
yy PhacoOptics. selecting the correct axis for toric IOLs
A-constant as well as placement of limbal relaxing In this power calculation strategy,
A-constant, although called a constant is incisions (LRIs) for astigmatism anterior and posterior central curvature
actually highly variable depending upon correction. radii, asphericity of the surfaces, central
multiple factors – IOL dependent: type, The first commercially available IOL thickness, and index of refraction
material, position; surgeon dependent: intraoperative wavefront aberrometer are all used to describe the IOL.
technique of incision, placement was the ORange (WaveTec Vision),
of incision; K and AL measurement which was later updated to the A problem for both strategies, Gaussian
adjustments; or even adjustment for the Optiwave Refractive Analysis (ORA) and ray tracing, is that the postoperative
manner of carrying out biometry. Once system (Alcon). This device projects position of the IOL cannot be
fixed for a particular surgeon, IOL and light onto the retina, and the reflected determined before surgery. Therefore,
machine for the scan, it is applied as a images pass through the optical system ray tracing is no more advantageous
constant to the appropriate formula. It of the eye, distorting its wavefront, than third-generation IOL formulas to
approximately varies with a ratio of 1:1 which is subsequently analyzed predict the accuracy of postoperative
with the IOL power1,2. according to optical and mathematical IOL position.
principles proprietary to the device.
Recent Advances Which are The ORA system takes into account Recent Formulas
Gaining Importance are: both the anterior and posterior corneal The Olsen formula and the
Intraoperative aberrometry astigmatism, which may improve C-Constant
astigmatic outcomes by accounting
One of the latest developments in optical for refractive contribution from the The Olsen formula uses exact ray
biometry is intraoperative wavefront posterior cornea. tracing and thick lens considerations
aberrometry. This technology provides There are several potential issues to account for the true physical
real-time intraoperative refractive with the use of IA. The fact that dimensions of an eye’s optical system.
information to increase the precision measurements taken during surgery do It uses the same technology employed
and accuracy of IOL selection under not reflect the postoperative state of the by physicists to design telescopes and
aphakic and pseudophakic conditions eye can introduce inaccuracies in power camera lenses. A key feature of the Olsen
after removal of a cataractous lens in calculation. formula is accurate estimation of the
normal eyes, post–refractive surgery IOL’s physical position using a newly
developed concept, the C-constant. The
C-constant can be thought of as a ratio
by which the empty capsular bag will
encapsulate and fixate an IOL following

54 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

Monthly Meeting Update

Table 1- Different constants that are used for different formulas are shown in table below.

Formulae Paramatters Used Intermediat Factor Details of the Parameter Recommendation
to Arrive at ELP

SRK/T AL and corneal power A contant Optimization consist of (1) Normal and long eyes
post operative ACD (2) A retina
thickness correcdtion factor
and (3) corneal refractive index

Haigis AL and ACD Three variable a0 a1 The a1 contant tied to the Hiaigs (a0 optimized
and a2 measured ACD, while only) normal eyes Haigis
a2 constant is tied to the (a0, at a2 optimized);
measured AL short long eyes

Hoffer Q AL and corneal power personalized ACD, (1) A factor tied the increases The hoffer Q formula
(pACD) the ACD with AL (2) A factor should be for eyes
that increases the ACD with measuring <22 mm,
corneal curvature (3)a factor according to the Royal
that modrates the change in Collge of Ophthamology
ACD for extremely long and guidelines
short eyes and (4) a constant
added to the ACD

Holladay 1 AL and corneal power Surgeon factor Distance from the post The holiday 1 is
oprative anterior iris place to reccomended for eye
the effective optical plane of measuring between 24.5
the IOL to 26.0 mm

Holladay 2 AL, corneal power, Anterior chamber 2 parameter used to calculated Reccomanded for short-
ACD, lens thickness depth ACD long eyes including for
(optional), age meniscus IOLs designs
(optional), white to
in the low plus to minus
white corneal diamter power range

(optional)

Olsen Lens thickness C contant Lens thickness together with Small to long eyes
together with ACD anterior chamber depth by ray
teacing technique

Burrett AL, corneal power, Lens factor The Barrett formula is
ACD (optional) lens reccomanded for short-
thickness (optional), long eyes
white to white corneal
diameter (optional)

in-the-bag implantation. This approach science of IOL power calculation to the IOL power prediction.
predicts the IOL position as a function the next level and eliminates the
of preoperative anterior chamber shortcomings of second-generation IOL Kane Formula
depth and lens thickness. Because calculation formulas. It incorporates The Kane formula was developed in
this approach works independent of the C-constant concept to predict IOL September 2017 using ~30,000 highly
traditional factors such as eye length, position after surgery. In addition to accurate cases. The formula is based on
keratometry (K), white to white accurate K readings and axial length theoretical optics and incorporates both
dimension, IOL power, age, and gender measurements, the keys to success regression and artificial intelligence
it can work in any type of eye, including with the Olsen formula are accurate components to further refine its
those that have previously undergone preoperative measurements of the predictions. The formula was created
refractive surgery. Its only requirements position and thickness of the crystalline using high-performance cloud-based
are accurate measurements of anterior lens, leading to an unbiased prediction computing which is a way to leverage
chamber depth and lens thickness. of the IOL position-the very heart of any the power of the cloud to create a virtual
So, The Olsen formula takes the IOL calculation-and, consequently, of supercomputer capable of performing

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Monthly Meeting Update

many decades’ worth of calculations in from over 17 countries. The Hill-RBF is The adjustment of measured ALs has
a few days. A focus of the formula was incorporated in Lenstar Eye Suite and been suggested as another method
to reduce the errors seen at the extremes is also available to ophthalmologists to correct for systemic inaccuracies
of the various ocular dimensions which globally as an open access web-based in long eyes. In 2011, the Wang-
is where the current formulas display calculator (rbfcalculator.com/online). Koch method for optimization of IOL
larger errors. Variables used in the The uniqueness of Hill-RBF lies in the formulas with long ALs was developed
formula are axial length, keratometry, fact that greater the number of surgical and validated. Upon validation of the
anterior chamber depth, lens thickness, outcomes that are fit into the model, Wang-Koch approach, the authors
central corneal thickness and patient greater the accuracy. In other words, found that the mean numerical errors
gender the more the number of eyes added with optimized ALs were significantly
to database, the more accurate the reduced compared with the mean
Barrett Universal (Barrett U2) calculator becomes. The new Hill-RBF numerical errors with partial coherence
The formula is called Universal because method is an advanced, self-validating interferometry.
it is suitable for all types of eyes: short, method for IOL power selection. It was
medium, or long and also for different launched in 2016. It is purely “data Wang and Koch optimization
lens styles. This formula is based on a driven,” independent of ELP and has yy 26 mm; 7% of eyes.
theoretical model of eye in which ACD no data bias. RBF method uses artificial yy Accuracy can be improved by
is related to AL and K. In this formula, intelligence-driven pattern recognition
ELP is characterized by ACD and LF and sophisticated data interpolation. modifying the AL value entered
(lens factor). The LF is influenced by K, The older version of Hill RBF online in 3rd-gen theoretical “thin-lens”
AL, ACD, LT, and WTW in that order. calculator used data from 3400 eyes formulas as it overcorrects the
This formula also takes into account the with a wide range of preoperative ocular hyperopic outcomes and result in
negative value of LF in calculating ELP parameters. The RBF calculator has myopic errors.
in the presence of negative-powered been updated in 2017 and includes data yy 1-center study regression more
type of IOL. Following are the features from 12400 eyes. The data for normal aggressive more myopia.
of Barrett Universal II formula: eyes have been increased by about 7000 yy 2-center study less aggressive
eyes. A total of 1000 exceptionally short overcorrection slightly less.
yy Accurate for all eyes regardless of AL eyes and axial myopia with IOL power yy H1 2-center optimized AL = 0.8814 ®
yy Essential variables required for up to -5D have now been included in the IOLMaster AL + 2.8701.
latest version. In addition, a target other yy Haigis 2-center optimized AL =
calculation are AL, K, optical ACD, than plano can be set (e.g., surgeon can 0.9621 ® IOLMaster AL + 0.6763.
and desired postoperative refraction. aim for slight myopia and calculate the yy SRK/T 2-center optimized AL =
Optional variables required are LT required IOL power accordingly). 0.8981 ® IOLMaster AL + 2.5637.
and WTW yy Hoffer Q 2-center optimized AL =
yy Lens factor or “A constant” of the Wang-Koch formula for 0.8776 ® IOLMaster AL + 2.9269.
selected IOL is required. If not optimization of intraocular lens yy Nonlinear Regression equation.
available, ULIB “A constant” of power calculation yy Used 14,000 cases to generate
SRK/T formula is recommended nonlinear equations for both the
(ULIB is the User Group for Laser In eyes with long ALs, IOL formulas Holladay I and II formulas in long
Interference Biometry) might not consistently produce eyes.
yy AL and K data from optical biometer accurate results. Hyperopic error can yy Regression produces myopic error.
(for example, IOLMaster, Lenstar) is be found after IOL implantation in long yy The regression begins at 24 mm-the
required for calculation. eyes. Wang et al. have hypothesized that arithmetic mean of the AL & has no
yy Barrett U2 is able to predict for highly this hyperopic error is attributable to1 as upper limit.
myopic eyes and negative powered AL increases, inaccurate estimation of yy Two regressions referred to as the
IOLs without specialized constants ACD in the determination of effective ‘1-center’ and ‘2-center’ regressions.
or AL modification. lens position;2 in optical biometry, yy 1-center regression-more aggressive,
Hill-Radial Basis Activation Function a single value used for the refractive myopic error, recommended.
(radial basis activation function online index that converts optical path length yy 2-center’ regression-less aggressive,
calculator) to AL, despite a different refractive equal myopic and hyperopic errors.
index of vitreous because of vitreous yy 2 centre optimized AL = 0.8814 ®
The Hill-RBF is the product of the liquefaction in long eyes; and3 in US
efforts of Dr Warren Hill and his biometry, inaccurate measurement
team which included engineers from of AL in the presence of posterior
MathWorks, and 39 investigators staphylomata, which are common in
long eyes.

56 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

Monthly Meeting Update

Figure 2. Accuracy range of commonly used formulas by axial length. double every 5-10 years. We are now
on the verge of a level of accuracy
IOLMaster AL +2.8701. yy Validate your measurements: Best for refractive outcomes never before
Dr Holladay has created a chart that way to check the accuracy of your seen in Ophthalmology. But to
illustrates this point. “You can divide measurements is by using validation fully enjoy this, we all have to use
eyes along two axes: the axial length criteria .Both Zeiss and Haag-Streit validated measurements. Work with
and the size of the anterior segment,” have validation criteria available properly optimized lens constants.
he says. “That leaves you with nine for the IOL Master and the LenStar, Adapt to new technologies as they
categories, ranging from long eyes with respectively, so the technician present and strive to use all available
shallow anterior segments to short eyes should take the measurements and resources to their best advantage.
with deep anterior segments. apply the validation criteria before
If the eye having normal anterior letting the patient go References
segment size, 80% of these may be
having short axial length and 90% may yy Don’t remove yourself from the 1. Fedorov SN, Kolinko AI, Kolinko AI.
be having long axial length similarly if process Physician is the most [Estimation of optical power of the
the patient eye is having normal axial knowledgeable person on the intraocular lens] [Russian]. Vestn
length then 2% may be having short team .Staff needs to look at the Oftalmol 1967; 80:27–31.
anterior segment and 2% eye may be measurements and make sure
having large anterior segment size. they’re right, but the final arbiter 2. Wang L, Tang M, Huang D, Weikert
making the final decision regarding MP, Koch DD. Comparison of newer
Summary IOL calculations needs to be the intraocular lens power calculation
To arrive at accurate results in biometry physician methods for eyes after corneal refractive
for IOL Power calculation & prevent surgery. Ophthalmology 2015;
significant Refractive surprises, it is yy Spend extra time counselling 122:2443–2449. Available at: https://
advised to follow the following steps: patients with short eyes or previous www. ncbi.nlm.nih.gov/pmc/articles/
yy Optimize your lens constants: refractive surgery. PMC4658226/pdf/nihms730050.pdf.
Accessed May 31, 2017.
Lens constants provided by the These patients are most likely to have
manufacturer can be more than a refractive surprise. “These patients 3. Hoffer KJ. The Hoffer Q formula: a
a half-diopter different from a need to understand that their eyes fall comparison of theoretic and regression
surgeon’s own lens constants. To into a category in which it’s difficult to formulas. J Cataract Refract Surg 1993;
improve your outcomes, optimize guarantee a perfect outcome 19:700–712; errata, 1994; 20:677.
your lens constant
yy Improvements in technology have 4. Hoffer KJ, Aramberri J, Haigis W, Olsen
allowed accuracy of Biometry to T, Savini G, Shammas HJ, Bentow S.
Protocols for studies of intraocular
lens formula accuracy [editorial]. Am J
Ophthalmol 2015; 160:403–405.

5. Frank W. Howes, Patient Workup
for Cataract Surgery: Chapter 5.3,
Ophthalmology, 4th Edition | Myron
Yanoff, Jay Duker

6. Holladay JT. Standardizing constants
for ultrasonic biometry, keratometry,
and intraocular lens power calculations.
J Cataract Refract Surg. 1997;23(9):1356-
1370.

7. Holladay JT, Prager TC, Ruiz RS, Lewis
JW, Rosenthal H. Improving the
predictability of intraocular lens power
calculations. Arch Ophthalmol 1986;
104:539–541.

8. Preussner P-R, Wahl J, Lahdo H, Dick B,
Findl O. Ray tracing for intraocular lens
calculation. J Cataract Refract Surg 2002;
28:1412–1419.

9. Olsen T, Hoffmann P. C constant:
new concept for ray tracing–assisted
intraocular lens power calculation. J
Cataract Refract Surg 2014; 40:764–773.

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Monthly Meeting Update

10. Hoffmann PC, Wahl J, Preußner P-R. 14. Abulafia A, Barrett GD, Rotenberg M, Corresponding Author:
Accuracy of intraocular lens calculation Kleinmann G, Levy A, Reitblat O, Koch
with ray tracing. J Refract Surg 2012; DD, Wang L, Assia EI. Intraocular Dr. J.S. Bhalla MS, DNB, MNAMS
28:650–655. lens power calculation for eyes with Deen Dayal Upadhyay Hospital, Hari Nagar,
an axial length greater than 26.0 mm: New Delhi, India.
11. Olsen T, inventor; IOL Innovations comparison of formulas and methods. J
APS, assignee. Method and uses. Cataract Refract Surg, 2015. 41(3): p. 548-
Predicting the post-operative position 56.
of a replacement intraocular lens. UK
patent application GB 2488802. 2012. 15. Wang L, Shirayama M, Ma XJ, Kohnen
Available at: http://me2.ipo.gov.uk/p- T, Koch DD. Optimizing intraocular
find-publication-getPDF.pdf? lens power calculations in eyes with
axial lengths above 25.0 mm. J Cataract
13. Hill W. Hill-RBF Calculator. 2016; Refract Surg 2011; 37:2018–2027.
Available from: http://rbfcalculator.
com.

Rakesh Pandey After

(Ocularist) www.dosonline.org/dos-times

Before

58 DOS Times - Volume 25, Number 1, July - August 2019

PG Corner - Essay type Question

Fungal Keratitis

Deepali Singhal1 MD, Prafulla Kumar Maharana2 MD, Namrata Sharma2 MD
1Eye-Q Super-speciality Eye Hospital, Max Multi-specialty Centre, Noida, Uttar Pradesh
2Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

Mycotic keratitis is a leading cause Table 1. Risk factors for the
of ocular morbidity in developing development of fungal keratitis.
countries1–3.
Fungal keratitis Ocular factors
constitutes up to 50% of all microbial Trauma
keratitis worldwide3–6. The commonly Chronic corneal inflammation
involved pathogens in tropical areas yy Herpes simplex
are filamentous fungi (Aspergillus, yy Herpes zoster
Fusarium, and Curvularia), while in yy Vernal allergic conjunctivitis
temperate regions are Candida species yy Ocular surface problems
(C. albicans, C. parapsilosis). yy Dry eye
Figure 1. A case of fungal keratitis following yy Bullous keratopathy
The management and diagnosis of trauma with vegetative matter. yy Exposure Keratopathy
fungal keratitis is quite challenging. yy Contact lens wear
This may be due to the lack of early Figure 2. A case of post LASIK fungal yy Drugs
microbiological identification and keratitis with culture positive for Fusarium Corticosteroids
limited efficacy and penetration of sp. Anesthetics
the anti-fungal agents7-9. In cases to 50 years with males being more Corneal surgery
with failed medical management commonly affected as compared to yy Penetrating Keratoplasty
surgical interventions like therapeutic females. A higher incidence has been yy Refractive surgery
keratoplasty (TKP), conjunctival flap, reported during monsoon and early Systemic factors
lamellar keratoplasty or cryotherapy winter due to high humidity along Diabetes mellitus
are required for control of infection and with more frequent vegetative injuries HIV positive patients
visual rehabilitation8,10,11. during these seasons17. Leprosy
Risk factors Adapted from Fungal keratitis. In:
Epidemiology Various factors predisposing to fungal Sharma N, Vajpayee RB (eds). Corneal
The incidence of fungal keratitis varies keratitis can be divided as ocular and ulcers: Diagnosis and management,
according to geography, climate and systemic. The most common ocular chap. 16. Jaypee, 2008.
occupation. In the developed countries risk factor is trauma with vegetative
the incidence has been estimated to or organic matter (Figure 1). 16 Other Etiopathogenesis
be as low as 6-20%12. However, in ocular factors associated include Fungal pathogens involved in
developing countries it is reported to be contact lens wear, medications and infective keratitis can be classified into
50% of all microbial keratitis13. prior ocular surgery (Figure 2) (Table 1). four classes – Filamentous septate,
Filamentous non-septate, yeasts and
Most commonly isolated fungal
pathogens are the filamentous fungi
worldwide with Aspergillus species (sp.)
being the most common14. In India, the
most commonly isolated organism in
south is Fusarium sp. while in northern
India is Aspergillus sp15,16.

It is more commonly seen in tropical
areas with warm and humid climate.
The most common age group is 21

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others (Table 2). These organisms Table 2. Fungi causing human
can also be classified into four keratitis.
groups: Moniliaceae (nonpigmented
filamentary fungi including Fusarium I. Filamentous
sp and Aspergillus sp); Dematiaceae
(pigmented filamentary fungi including A. Septate
Curvularia sp and Lasiodiplodia sp);
yeasts, including Candida sp; and other 1. Nonpigmented
fungi.
Fungi are either saprophytic, or yy Fusarium solani, oxysporum,
pathogenic organisms. Many fungi moniliforme, episphaesia, nivale
associated with keratitis are saprophytic.
These organisms often invade into the yy Aspergillus fumigatus, flavus
corneal stroma following epithelial
defect that may be caused by various yy Acremonium (Cephalosporium)
risk factors mentioned above. After
invasion, they proliferate and incite an yy Paecilomyces Figure 3. A case of fungal keratitis showing
inflammatory reaction, which leads to feathery margins with a fixed hypopyon of
tissue necrosis. They can also penetrate yy Penicillium 1 mm.
through an intact Descemet membrane
(DM) gaining access into the anterior 2. Pigmented (Dematiacious) Table 3. Presenting clinical
chamber from where it is often difficult features of fungal keratitis.
to eradicate. Blood-borne growth yy Curvularia senegelensis, Nonspecific
inhibiting factors may not reach the verruculosa, pallescens yy Conjunctival injection
avascular tissue such as the cornea, yy Epithelial defect
anterior chamber and sclera, and hence yy Lasiodiplodia theobromae yy Anterior chamber reaction
the fungi continue to multiply and Specific
persist despite treatment. yy Alternaria yy Deep stromal infiltrate
yy Feathery margins
Clinical features (Table 3) yy Cladosporium yy Gray/brown pigmentation
The clinical diagnosis of fungal keratitis yy Elevated edges
is often challenging. It should be made yy Celletotrichum yy Dry looking with rough texture
on the basis of a careful evaluation yy Satellite lesions
of patient’s history, examination and yy Drechslera (Helminthosporuim) yy Lack of cornea sensation
laboratory investigations. Adapted from Groos Jr EB. Fungal
B. Nonseptate keratitis. In: Miller D, Galor A, Alfonso
General symptoms EC (eds). Cornea: Fundamentals of
A patient with fungal keratitis often Rhizopus (mucormycosis) Cornea and External Disease, chap. 80.
presents with insidious onset of foreign Mosby: St Louis, MO, 1997.
body sensation with photophobia, II. Yeast
gradually progressive pain and Laboratory diagnosis
diminution of vision. The patient gives yy Candidia albicans, parapsilosis, The next step after clinical examination
a long duration of history of these krusei, tropicalis of a corneal ulcer is corneal scraping
symptoms, which are much less than which plays an important role in
the ocular signs. Adapted from Fungal keratitis. In: diagnosis. Scraping should be taken
Sharma N, Vajpayee RB (eds). Corneal from the base as well as the edge of the
General signs ulcers: Diagnosis and management, chap. ulcer with the help of a surgical blade,
On slit lamp examination, a fungal 16. Jaypee, 2008. Kimura’s spatula or a 26 guage needle.
ulcer characteristically appears to have Calcium alginate swab, Dacron/rayon
a dry texture with gray white infiltrates Presence of a fixed hypopyon (no swab or sponge type material can also
and creamy raised exudates at the base. change in the position after 10 minutes be used. Other important samples could
The characteristic findings include of lying supine) is also a common
feathery margins (70%) with elevated feature seen in 45-66% cases (Figure 3).
areas and satellite lesions (10%)18,19. Other features include an immune ring,
deep stromal abscess and an endothelial
plaque (Figure 4).
Candida keratitis often presents
with “collar button” configuration
of infiltrates and dematiacious
fungi have a characterisitic gray or
brown pigmentation (Figure 5). This
pigmentation is due to the alteration
in melanin metabolism and indicates
a more superficial infection with low
virulence of the organism and less
inflammatory reaction20.

60 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

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Figure 4. A case of fungal keratitis showing This is the gold standard method for structures are 10–40 micrometers in
a central endothelial plaque of 2 x 1.5 mm diagnosis and takes around two weeks length and 5–10 micrometers in width26.
in size. duration for the result.
Confocal microscopy has a sensitivity
Figure 5. A case of Curvularia keratitis Diagnosis of fungal keratitis is made if of 94% and a specificity of 78% in
showing central pigmented infiltrates. patients with fungal keratitis.27
be contact lenses and solutions used yy Smear is positive for fungal elements IVCM also allows determination of
by the patient, any topical medication yy Fungal growth is positive in more the depth of infection, which is an
or cosmetic agents. In cases with deep important prognostic factor. Main
stromal abscess without any epithelial than one medium if there is absence limitation is that it remains extremely
defect, anterior chamber tap or corneal of fungus in smear. user dependent, as the testing requires
biopsy can be taken. The sample yy Fungus grows on a single medium in a skilled operator, and interpretation
obtained should be sent for direct the presence of fungus in smear. requires an experienced viewer.
microscopy and culture examination. yy Confluent growth at the inoculated Therefore, corneal cultures remain the
Direct microscopy site on a single solid medium. gold standard for diagnosis.
This includes 10% KOH wet mount The incidence of culture positivity
preparation, which is rapid, cheap and is reported to be 52-68%24. Before Anterior segment optical
easily available and has a sensitivity of declaring a culture negative for fungi coherence tomography
72-90%21,22. it is recommended to wait for at least a Spectral domain anterior segment
Other staining methods used are Gram duration of two weeks. Increasing the optical coherence tomography (SD-
stain (31-98% sensitive), Giemsa stain humidity of the medium by placing the ASOCT) has been reported to be useful
(27-87%), Lactophenol cotton blue (70- inoculated agar plates in plastic bags in fungal keratitis by the authors.28
80%), Grocott’s methenamine-silver can enhance fungal growth. This noncontact imaging modality
staining (89%) and Calcofluor white provides cross-sectional imaging of the
stain (80-90% sensitive)23. Other diagnostic modalities cornea and quantitative assessment
Fungal culture Polymerase Chain Reaction of the depth of stromal infiltrates as
Sabouraud’s dextrose agar is commonly well as the width of the infiltrates
used for fungal culture. It should This technique provides a rapid along with measurement of corneal
contain 50 micrograms /ml gentamicin diagnosis with an early initiation thickness. SD-ASOCT was found to
and should be without cycloheximide of antifungal therapy. The result be extremely useful for identification,
as this inhibits saprophytic fungi. is obtained within 4 hours, which measurement, and monitoring of the
can make this technique a valuable size and margin of the ulcer, depth and
adjunctive tool for the diagnosis of extent of infiltrates, and measurement
fungal keratitis of CT even in the presence of corneal
edema. Certain specific features of
Confocal Microscopy fungal keratitis such as satellite lesions,
In vivo confocal microscopy (IVCM) drug deposits, endothelial plaques,
is emerging as a tool for early and stromal necrotic areas, which are
identification of fungal elements due often difficult to detect on slit-lamp
to its property of providing optical examination, could be identified easily
sections with a better resolution and on ASOCT. Thus, SD-ASOCT can be
contrast. Aspergillus hyphae are seen used as an adjunctive tool for objective
as septate with a diameter of 5–10 assessmentandquantitativemonitoring
micrometers and 200–400 micrometers of patients with fungal keratitis with
long with dichotomous branching at greater accuracy. However, it must be
45 degrees angle. In contrast, Fusarium emphasized that it is not an absolutely
typically branches at a 90degree angle25. essential tool for management of
These hyper-reflective elements must fungal keratitis, but if available, it is an
be differentiated from the basal corneal extremely useful adjunctive tool for the
epithelial nerves, which have a more treating physician.
regular branching pattern. Stromal
nerves, on the other hand, are much Management
larger in diameter (25–50 micrometers). The management options include
In addition, yeast such as Candida medical therapy and surgical
albicans have round, budding bodies intervention in cases not responding to
that may develop pseudohyphae. The

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PG Corner - Essay type Question

medical therapy alone. The authors have Systemic antifungal Topical NTM 5%
described a topical systemic targeted (KCZ/VCZ) (n=223)
therapy (TST) protocol, which provides (n=117)
a stepwise treatment algorithm for 7.10 days Severe corneal thinning/
management of fungal keratitis with 1. Size of ulcer >5mm Good response impending perforation/
varying severity (Figure 6)29. 2. Depth of ulcer >50% Poor response perforation

Medical management Continue NTM 5% Add Topical VCZ 1%
Anti fungal drugs should be started once (n=83) 9n=135)
the corneal scraping sample is detected
positive for fungal elements or fungal 7.10 days
culture is positive at 36-48 hours. It is
not recommended to start anti fungal Good response Poor response
treatment empirically on the basis of
clinical examination. Continue NTM 5% + Intrastromal/ Therapeutic
VCZ 1% Intracameral/Both- Keratoplasty
Medical management includes either (n=25) antifungal injection
topical or systemic anti fungal agents. (n=45)
The antifungal drugs can be broadly (n=82)
classified into different categories
based on their molecular structure Good response Poor response Poor
and mechanism of action. They response
are broadly classified as polyenes, Continue NTM 5% + Repeat upto 3-4
azoles, pyrimidines, allylamines, VCZ 1% intrastromal injections
echinocandins, heterocyclics and others (n=73) at intervals of 72 hours
(Table 4).
(n=8)
Topical Antifungal Agents
The initial drug of choice in fungal Good response
keratitis is 5% natamycin suspension.
It is the only US FDA approved topical Figure 6. Topical systemic targeted therapy protocol for fungal keratitis.
antifungal drug for mycotic keratitis
and is commercially available for is recommended to continue topical and increase penetration of antifungal
ophthalmic use at a concentration medication for at-least 2 weeks after the agents in cases with epithelial plaque or
of 5% (50mg/ml). It is recommended resolution of infection. drug deposits (Figure 7a,7b,8).
to start topical natamycin 5% every If there is worsening even with topical
one hourly, for first 48 hours and natamycin, other agents can be started The features indicating the response to
then two hourly during waking hours according to the species isolated. treatment include reduction in pain,
till epithelial healing and then four Topical amphotericin B 0.15% or size of infiltrates and epithelial defect,
hourly for three weeks. In addition, topical fluconazole 0.3% are preferred disappearance of satellite lesions,
cycloplegics have to be prescribed in for yeast organisms. Topical econazole rounding of feathery margins and
the form of topical homatropine 2% 1% has been reported to have a similar vascularization (Figure 9). The duration
four times a day. We also recommend efficacy as natamycin 5%30. of treatment is longer as compared to
starting a broad-spectrum antibiotic A newer agent that can be used topically bacterial keratitis (around 4-6 weeks).
such as a fluroquinolone to prevent is voriconazole. It is derived from
secondary bacterial infection. Anti fluconazole and acts by inhibition of Systemic antifungal therapy
glaucoma medication should be added cytochrome P450- dependent 14 alpha Oral antifungal therapy is recommended
in cases with high intraocular pressure sterol demethylase, an enzyme involved in cases of severe keratitis. Harrison et
(IOP). in the ergosterol biosynthesis31. It has a al described the grading of a corneal
broad spectrum of action and can inhibit ulcer as mild, moderate and severe
These patients have to be examined both yeast and filamentous fungi. The on the basis of size and depth of ulcer,
twice daily to monitor the response of minimal inhibitory concentration infiltrate density and extent and scleral
treatment. The frequency of topical of voriconazole (0.5 μg/ml) is less as involvement33. Severe ulcers are defined
natamycin can be decreased to compared to other imidazoles32. Topical as >5mm in size, >50% depth with dense
2-hourly once resolution starts and is voriconazole 1% is preferred in cases infiltrates deeper than mid stroma with
continued till complete resolution. It of recalcitrant fungal keratitis, which or without scleral involvement. Other
are refractory to topical natamycin and indications of oral therapy include
amphotericin B therapy. scleral or limbal involvement, bilateral
Epithelial debridement might help to ulcers, endophthalmitis, pediatric cases,
accelerate the resolution of infection impending perforation or perforated
corneal ulcer, recalcitrant mycotic
keratitis and post keratoplasty cases.

62 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

PG Corner - Essay type Question PG Corner - Essay type Question

Table 4. Common antifungals for medical therapy of fungal keratitis.

Drug Mechanism Spectrum of Routes of administration
action

Topical Oral Intravenous Intrastromal Intracameral

Polyenes Binds to fungal Amphotericin: 0.05-0.3% NA 0.5-0.7 mg/kg 0.8-1.0 mg
Amphotericin B cell First line therapy (0.15% Not Not available
membranes, for Candida commonly available
Natamycin altering species. Good used)
(Pimaricin) membrane to moderate
permeability activity against 2.5-5%
Concentration Aspergillus,
dependent Fusarium species
killing
Fungicidal or Natamycin: Good
fungistatic activity against
depending most Fusarium,
on the Aspergillus,
concentration less effective
In vivo efficacy against Candida
best: AUC/MIC ≥ species; first-
25 and/or Cmax/ line treatment
MIC ≥10 for fungal
Optimal keratitis, 2%
frequency bioavailability
for topical
administration
undetermined
Recommended
dosing: Initial
loading dose
of one drop
every half hour
with a gradual
reduction to six
to eight times
a day
Do not penetrate
intact epithelial
barrier

Azoles Inhibitor of
ergosterol
biosynthesis of
the fungal cell
wall, through
action on the
cytochrome P-
450- dependent
enzyme. This
leads to cell
membrane
destabilization
and leakage
Concentration
independent
killing (Time
dependent)
Mainly
fungistatic; can
be fungicidal
at high
concentrations
or growth phase
w6w2w.doDsOonSliTniem.oersg/-dVoosl-utimmoefets2h5e, Nfuunmgbier 1, July - August 2019
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In vivo efficacy:
AUC/MIC >25
Two classes:

enzyme. This

leads to cell
membrane
PPGG CCoorrnneerr -- EEssssaayydatnetysdytpaplebeeaiklQiQazgauuetieeosnsttiioonn

Concentration

independent
anMMdfktueiilanfepluiicgennnhinlsgygdata(neaTtnliiissctm)m;fcoearnmediSaccpatelicotthnreurmapoyfof
Table 4. Common fungal keratitis.
Drug
Routes of administration

be fungicidal Topical Oral Intravenous Intrastromal Intracameral

Polyenes cdBfFkmacIRuadpCffOomb2MAie(Tve(k•pomiiw•cGnIpoantnorufcnneooppldt5uoneefreTIiieeeonowelroeUoplterlneeimttInlunnppsmrthaiinrtcosnegtvvrlqdcnlaaaColttttmmootmhiCtdicgcocileeccrteiiroiihphhugneccc:nidocaicgmovroviosieonneemdt/≥cAttntonibbeeeneeeedszpiog1Mrhoonnnncnewltaddmfntnccnnllaorraiaa/Ugian0moiruiiaaatzstaaaoeiooceebzdlttleIatcuusmrrnatatozzznCennniarChffrforrstiyzaaaeriommzzufofoaogsllnnrlecgaeetloi/Clnttiiieoonpat>ellnMlnccsiiseetitloieseedmooltl):yvih2aa,eoaaegeoee),.ro,enIncce5dl.ana,D,afCandyyrsslnxyoe:≥/d Amphotericin: 0.05-0.3% NA 0.5-0.7 mg/kg 0.8-1.0 mg
Amphotericin B First line therapy (0.15% Not Not available
for Candida commonly available
Natamycin species. Good used)
(Pimaricin) to moderate
activity against 2.5-5%
Aspergillus,
Fusarium species

Natamycin: Good
activity against
most Fusarium,
Aspergillus,
less effective
against Candida
species; first-
line treatment
for fungal
keratitis, 2%
bioavailability

Clotrimazole dosing: Initial Clotrimazole: 1% topical
loading dose Fungistatic 1% cream
of one drop
Good activity
every half hour against Candida
with a gradual and some
PG Corner - EssaryedtuycptieonQtouseisxtionAspergillus
to eight times species
a day
Do not penetrate Econazole: 0.02-2% 50-100
Minteaccht aenpitshmelial EAFSaucfpsftpseeiaeccorrttniigruvuimellmua, gso,aafinnsdt mg/day Routes of administration
Drug barrier

Azoles Inhibitor of Candida species Topical Oral Intravenous Intrastromal Intracameral
ergosterol
Ketoconazole biosynthesis of Ketoconazole: 1-2% 200-400
Effective against 1% mg/day
the fungal cell Candida, 63
www.dosonline.org/dos-timweasll, through Aspergillus, DOS Times - Volume 25, Number 1, July-August 2019
limited
action on the effectiveness
cytochrome P- against Fusarium
450- dependent species.
ltraconazole:
enzyme. This Aspergillus,
leads to cell Candida species,
Itraconazole membrane not effective 200-400
against Fusarium mg/day
destabilization
and leakage
Concentration
independent
killing (Time
Fluconazole dependent) Fluconazole: 0.5-1% 100-400
Effective against mg/day
Mainly yeast, minimal
fungistatic; can activity against
be fungicidal filamentous
at high
concentrations fungi
or growth phase
Miconazole VVoolluummoeef 2t2h55e,,NNfuuumnmgbbieerr11,,JJuullyy Miconazole: 1% 600 - 1200 / day 5 mg / 0.5 ml
In vivo efficacy: Effective against
6642 DDOOSSTTiimmeess -- AUC/MIC >25 -P-AaAueugcguiulsosttm2200y11c9e9s, wwwwww..ddoossoonnlliinnee..oorrgg//ddooss--ttiimmeess
Two classes: Scedosporium
species

Effective against mg/day
Candida,
Aspergillus, PG Corner - Essay type Question
limited

PG Corner - Essay type Questioneffectiveness

against Fusarium
species.

ITtarabcloen4a.zCoolemmon antifungals for mediAltcrsaaplcetorhngeialrzlauopsle,y: of fun1g%al keratitis. 200-400 Routes of administration
Drug Mechanism CSpanecdtirduamspeocfies, mg/day

nacottieofnfective

against Fusarium Topical Oral Intravenous Intrastromal Intracameral

FPloulycoenneaszole Binds to fungal Fluconazole: 0.5-1% 100-400 0.5-0.7 mg/kg 0.8-1.0 mg
Amphotericin B cell fafEystAfFiuoopceiflmrrfanteamesimcsCgvptctioiiathl,eetiidnmsnyovne.detteaGireoinagadtruotihgaiameosciaenidirnansal:tpsty 0.05-0.3% mNAg/day 5 mg / 0.5 ml
membranes, Macitcivointyazaoglaei:nst (0.15%
Miconazole altering EAfsfpecetrigvielluags,ainst commonly 600 - 1200 / day 50 mg/0.1 ml
membrane PFauescairlioummyscpees,cies used)
Natamycin permeability sSNapccateeticdaviomietssypyocaigrniau:iGnmsotod 1% Not Not available
(Pimaricin) Concentration PmoossatcoFunsaazroiluem: , 2.5-5% available
dependent LAismpeitregdillus, 200 mg
killing ilnesfsoremffeacttioivne, 1-2% x3/day
Fungicidal or hagaasibnesetnCuanseddida
fungistatic asps escaiveasg; efirrsets-cue 200-400 5 mg/ml
depending floinreFturseaartimumen,t mg/day
on the Sfocredfuonspgoalrium.
concentration Skpereacttirtuism, 2s%imilar
In vivo efficacy tboiovaovraiciloanbailziotyle
best: AUC/MIC ≥
25 and/or Cmax/ Voriconazole:
MIC ≥10 Fungicidal or
Optimal fungistatic
frequency depending on
for topical concentration
administration Candida species,
undetermined Aspergillus
Recommended species. non
dosing: Initial Fusarium
loading dose solani species,
of one drop Scedosporium
every half hour apiospermum
with a gradual
reduction to six
to eight times
a day
Do not penetrate

Echinocandins Binlotaccktsefpuinthgaelial Concentration dependent killing
cbealrlrwiearll beta
Fungicidal effective against yeasts, Aspergillus species; not effective against Fusarium species In
gInluhciabnitosyrnotfhesis vivo efficacy: best predicted by Cmax/MIC >10 or AUC/MIC >25
Azoles ergosterol
biosynthesis of
Anidulafungin the fungal cell Limited data
Capsofungin wall, through
Micafungin 0.5%
0.1%

Echinocandins Balcotciokns founntghael cell wall beta
gclyutcoacnhrsoymntehPe-sis
C4o50n-cdeenptreantdioenntdependent killing
Feunnzygmicied.aTlheifsfective against yeasts, Aspergillus species; not effective against Fusarium species In vivo efficacy: best
pleraedsicttoedceblyl Cmax/MIC >10 or AUC/MIC >25
64 DOS Times - Volummeem25b,rNaunme ber 1, July - August 2019
www.dosonline.org/dos-times
Cmax/MIC = peak concentrdaetisotnabovielirztahteiMonIC, >10; optimal dosing large infrequent doses, concentration dependent antifungals (polyenes, allyamines).
Natamycin is the only commaenrdcialellaykaavgaielable antifungal. All other ocular formulations are prepared extemporaneously. %T>MIC percent of the time above or near the
MIC; optimal dosing smalleCr omnocreefnretqruaetniot ndosing. AUC/MIC = average concentration over 24 hours; optimal dosing; concentration over time. Adapted and modified from
Groos Jr EB. Fungal keratitiisn. Idne:pMeinlledreDn,tGalor A, Alfonso EC (eds). Cornea: Fundamentals of Cornea and External Disease, chap. 80. Mosby: St Louis, MO, 1997.
killing (Time
dependent)
Mainly
fungistatic; can
be fungicidal
at high
concentrations
or growth phase
w6w2w.doDsOonSliTniem.oersg/-dVoosl-utimmoefets2h5e, Nfuunmgbier 1, July - August 2019
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In vivo efficacy:
AUC/MIC >25
Two classes:

PG Corner - Essay type Question

Figure 7a. A case of fungal keratitis showing Figure 7b. Resolving fungal keratitis with Targeted drug therapy
overlying drug deposits. central thinning after debridement of the Intracameral Therapy
drug deposits. Intracameral amphotericin B may be
Figure 8. Resolving Curvularia keratitis a useful modality in the treatment of
after epithelial debridement. Figure 9. Resolving fungal keratitis on deep stromal keratitis with associated
Some of the most commonly used medical therapy. anterior chamber reaction and
systemic antifungals are ketoconazole, photophobia and orthostatic recalcitrant mycotic keratitis that is not
itraconazole, fluconazole and more hypotension. Common adverse effects responding to topical natamycin38. Dose
recently voriconazole (VCZ)34-36. Oral of oral voriconazole include visual for intracameral use is 5-10 mcg / 0.1 ml
VCZ has been used as an adjunct to disturbances such as abnormal vision, and can be repeated at an interval of 72
topical NTM in the treatment of severe transient visual hallucinations or hours.
and recalcitrant mycotic keratitis and is confusion, color vision changes and
reported to have a high efficacy in such photophobia. This route of administration allows
cases35, 36. Posconazole (PCZ) is a second- adequate drug delivery into the anterior
It is important to evaluate liver function generation triazole similar to VCZ. It is chamber and may also help to avoid
tests every 2 weeks after starting a synthetic structural analog of ICZ and surgical intervention in acute keratitis.
ketoconazole. The duration of systemic has a broad-spectrum of action similar Voriconazole can also be administered
therapy is usually 6 to 8 weeks. Common to VCZ with activity against most through intracameral route in a dose
side effects of ketoconazole reported Candida spp. as well as fluconazole- of 50 mcg/ 0.1 ml. The advantage is
are hyperglycemia/hypertension, resistant isolates. PCZ has been shown that it has a broad spectrum of action
infertility in young people, QT to be effective against mycotic keratitis as compared to amphotericin B. The
prolongation, anaphylaxis, adrenal resistant to common antifungals like proposed limitations of intracameral
insufficiency, gynaecomastia, anorexia, KCZ, FCZ and VCZ. Altun et al reported antifungals are breach of natural barriers
hyperlipidemia, increased appetite, successful healing in two cases of of infection, deeper spread of infection,
insomnia, nervousness, headache, mycotic keratitis with topical (4mg/0.1 risk of iatrogenic spread to the site of
dizziness, paresthesia, somnolence, ml) and oral PCZ (200mg four times injection, intraocular inflammation,
daily), which were not responding to lenticular damage, glaucoma, hyphema
conventional antifungal therapy (NTM, and potential endothelial damage.
VCZ, fluconazole, and AMB)37.
Intrastromal Therapy
Intrastromal anti fungal injections have
similar indications as intracameral
therapy. They are mainly indicated
in deep stromal infections. VCZ is the
most commonly used antifungal agent
for intrastromal delivery. The other
antifungals include AMB and NTM.
Intrastromal VCZ provides a depot of
drug, close to the ulcerated area at a
dose of 50μg/0.1 ml in 5 divided doses,
from where the drug is slowly released
into the infected tissue. The method
of intrastromal injection described by
Prakash et al.39 is as follows: 50 μg /0.1
ml of the reconstituted VCZ solution
is loaded in a 1-ml tuberculin syringe
with a 30-gauge needle. The needle is
inserted obliquely into the cornea from
the uninvolved, clear area to reach just
flush to the ulcer at the mid stromal
level. Five divided doses are given
around the ulcer to form a deposit of the
drug around the circumference of the
lesion. This is done in such a manner

66 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

PG Corner - Essay type Question

that the injected drug appeared to slightly longer bites should be used challenge of fungal keratitis. Br J
surround the ulcer along each meridian. to avoid cheese wiring if the edge of Ophthalmol. 2011;95(12):1623–1624.
In cases of suboptimal response, three the recipient becomes involved. The
such injections can be given 72 hours anterior chamber should be irrigated 3. Thomas PA, Kaliamurthy J. Mycotic
apart. The major advantage is targeted to eliminate any organisms. The keratitis: epidemiology, diagnosis
drug delivery and also helps to avoid lens should be left intact to prevent and management. Clin Microb Infect.
penetrating keratoplasty in deep involvement of posterior segment. 2013;19(3):210–220.
stromal keratitis. The major limitation
of this method may be a further spread Any infected anterior segment structure 4. Leck AK, Thomas PA, Hagan M, et
of keratitis since performing any should be removed and sent for both al. Aetiology of suppurative corneal
intervention through normal cornea in microbiology and pathology for culture ulcers in Ghana and south India, and
presence of keratitis may lead to new and fixed section examination. An epidemiology of fungal keratitis. Br J
foci of infection. There is also a definite antifungal agent should be injected Ophthalmol. 2002;86(11):1211–1215.
risk of inadvertent anterior chamber which includes amphotericin B (5 μg/
entry while performing the procedure 0.1 ml) or voriconazole (50 μg/0.1 ml) in 5. Shokohi T, Nowroozpoor-Dailami K,
in a hazy cornea40. cases with suspected endophthalmitis. Moaddel-Haghighi T. Fungal keratitis
in patients with corneal ulcer in
Surgical management At the end of surgery both the Sari, Northern Iran. Arch Iran Med.
Tissue adhesives donor as well as the host specimen 2006;9(3):222– 227.
Cyanoacrylate glue can used to treat should be sent for histopathological
small perforations (less than 3 mm), examination. Fungal hyphae on 6. Zhong WX, Xie LX, Shi WY, et al.
progressive stromal keratolysis and pathological examination are usually Spectrum of infection of fungal keratitis:
descemetocele. The major advantage is seen parallel to the stromal lamellae analysis of 654 cases. Zhonghua Yi Xue
that it provides tectonic support along while if oriented perpendicularly are Za Zhi. 2006;86(24):1681–1685.
with an anti-bacterial action. However, indicative of increased virulence and
it is known to be toxic to the corneal poor prognosis41, 42. 7. Iyer SA, Tuli SS, Wagoner RC. Fungal
endothelium and incites stromal keratitis: emerging trends and
vascularization, which may become a After keratoplasty it is recommended treatment outcomes. Eye Contact Lens.
high risk factor for optical keratoplasty to continue the topical management 2006;32(6):267–271.
later. along with systemic agents if needed till
the histopathology report of the host 8. Rogers GM, Goins KM, Sutphin JE, et al.
Patch grafts specimen is available. If no organisms Outcomes of treatment of fungal keratitis
Patch graft is indicated in perforations are detected at the edge of the specimen, at the University of Iowa Hospitals and
of up to 5 mm diameter and is used anti-fungals could be stopped after Clinics: a 10-year retrospective analysis.
to remove the visible margin of the 2 weeks. However, if the specimen Cornea. 2013;32(8):1131–1136.
infected area. is positive for fungal organisms the
therapy should be continued for 9. Miller D. Pharmacological treatment
Therapeutic Keratoplasty duration of at-least 6 to 8 weeks. Topical for infectious corneal ulcers. Exp Opin
Therapeutic keratoplasty (TPK) is corticosteroids should be started with Pharmacother. 2013;14(5):543–560.
indicated in cases not responding or anti fungal cover, only if the specimen
worsening on medical treatment or is negative keeping in mind a risk of 10. Ansari Z, Miller D, Galor A. Current
cases with impending perforation or recurrence. thoughts in fungal keratitis: Diagnosis
large corneal perforation (>5mm). It and treatment. Curr Fung Infect Rep.
helps to maintain the integrity of globe To conclude, mycotic keratitis is an 2013;7(3):209–218.
as well as to control the infection. intricate and often a less rewarding
The prognosis of TPK is poor in cases disease entity to treat. A better 11. Ibrahim MM, Vanini R, Ibrahim
with involvement of limbus or sclera, understanding of the spectrum and FM, et al. Epidemiologic aspects and
endophthalmitis, and recurrent the pharmacokinetics of the available clinical outcome of fungal keratitis in
infection. antifungal drugs may help in improving southeastern Brazil. Euro J Ophthalmol.
the outcomes. 2009;19(3):355–361.
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fungal keratitis in North India. Cornea
2005;24:8–15

www.dosonline.org/dos-times DOS Times - Volume 25, Number 1, July-August 2019 67

PG Corner - Essay type Question

17. Hagan M, Wright E, Newman M, Dolin Sensitivity and specificity of confocal 37. Altun A, Kurna SA, Sengor T, Altun
P, Johnson G. Causes of suppurative scan in the diagnosis of infectious G, Olcaysu OO, Aki SF, Simsek MH.
keratitis in Ghana. Br J Ophthalmol keratitis. Cornea. 2007 Aug; 26(7):782– Effectiveness of posaconazole in
1995;79:1024-8. 786.] recalcitrant fungal keratitis resistant to
conventional antifungal drugs. Case Rep
18. Bharathi MJ, Ramakrishnan R, Vasu S, et 28. Sharma N, Singhal D, Maharana PK, Ophthalmol Med. 2014;2014:701653.
al. Epidemio- logical characteristics and Agarwal T, Sinha R, Satpathy G, Singh
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19. Srinivasan M, Gonzales CA, George C, 1394. Cornea 2002; 21:718-22.

et al. Epidemio- logy and aetiological
diagnosis of corneal ulceration in 29. Sharma N, Sahay P, Maharana PK, 39. Prakash G, Sharma N, Goel M, Titiyal JS,
Madurai, South India. Br J Ophthalmol Singhal D, Saluja G, Bandivadekar P, Vajpayee RB. Evaluation of intrastromal
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Satpathy G, Velpandian T. Management adjunctive for the management of
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40. Sharma N, Agarwal P, Sinha R, Titiyal
21. Vajpayee RB, Angra SK, Sandramouli S, 30. Prajna NV, John RK, Nirmalan PK, et al. JS, Velpandian T, Vajpayee RB.
Honavar SG, Chhabra VK. Laboratory A randomized clinical trial comparing Evaluation of intrastromal voriconazole
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1993;25:68-71. bjo.2010.192815.
31. Jeu L, Piacenti FJ, Lyakhovetskiy, et
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K, et al. Keratomyco- sis: clinical 2003;25:1321-81. Roussel TJ, Culbertson WW. Results
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isolates of Scedosporium apiospermum.
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Kaliamurthy J, Ackuaku E, John M, et al. 541-542.
Aetiology of suppurative corneal ulcers Corresponding Author:
in Ghana and south India, and epidemio- 34. Fitzsimons R, Peters AL. Miconazole
logy of fungal keratitis. Br J Ophthalmol and ketoconazole as a satisfactory first- Dr. Deepali Singhal
2002;86:1211- 5. line treatment for keratomycosis. Am J Eye-Q Super-speciality Eye Hospital, Max Multi-
Ophthalmol. 1986;101(5):605-608. specialty Centre, Noida, Uttar Pradesh, India
25. Florakis GJ, Moazami G, Schubert H, et
al. Scanning slit confocal microscopy 35. Freda R. Use of oral voriconazole as
of fungal keratitis. Arch Ophthal- mol adjunctive treatment of severe cornea
1997;115:1461-3. fungal infection: case report. Arq Bras
Oftalmol. 2006;69(3):431-434.
26. Labbe A, et al. Contribution of in vivo
confocal microscopy to the diagnosis 36. Jhanji V, Sharma N, Mannan R, Titiyal
and management of infectious keratitis. JS, Vajpayee RB. Management of tunnel
The Ocular Surface. 2009; 7:41–52. fungal infection with voriconazole. J
Cataract Refract Surg. 2007;33(5):915-
27. Kanavi MR, Javadi M, Yazdani S. 917. doi:10.1016/j.jcrs.2006.12.026.

68 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

Photoessay

Half in Half Out Nucleus in
Hypermature Cataract

Prafulla Kumar Maharana MD, Deepali Singhal MD
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

A 56-year-old male presented with Corresponding Author:
sudden onset painless diminution of
vision since 10 days in his right eye.
He had a history of gradual progressive
diminution of vision since 2 years.
There was no history of trauma, pain
or redness. Best corrected visual acuity
was hand motions close to face; the
intraocular pressure (IOP) was 16 mm
Hg. Cornea was clear with grade IV
nucleus sclerosis with fibrotic anterior
capsule suggestive of hypermature
cataract. It was dislocated into anterior
chamber with one-fourth still present in
patellar fossa. Intracapsular extraction
with anterior vitrectomy and peripheral
iridectomy was done in emergency.
Intraoperatively, a lax capsular bag
was suggestive of morgagnian cataract.
The postoperative day 7 visual acuity
was counting fingers at 2 metre with
IOP of 18 mm Hg. Anteriorly dislocated
lens should be removed as soon as
possible to minimize the risk of corneal
decompensation, secondary glaucoma
or posterior dislocation.

Dr. Prafulla Kumar Maharana
Dr. Rajendra Prasad Centre for Ophthalmic
Sciences, All India Institute of Medical Sciences,
New Delhi, India.

www.dosonline.org/dos-times DOS Times - Volume 25, Number 1, July-August 2019 69

DOS Times Quiz

DOS Times Quiz

July-August, 2019
What is your Diagnosis?

Pooja Shah MD, Rohan Chawla MD
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
A 56-year-old male, with no systemic illness presented with blurring of vision in right eye for 4 months. Visual acuity in the
right eye was 6/9p and left eye was 6/6. Anterior chamber was within normal limits and media was clear. Multimodal imaging
of right eye was as follows and left eye was normal.

70 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

DOS Times Quiz

Compiled by:

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

ANSWER
Answer _______________________________________________________________________________________________________________________________________
Name: ________________________________________________________________________________________________ Degree: _______________________________
Designation:_________________________________________________________________________ Address:_______________________________________________
_______________________________________________________________________ State _______________________________ Pin _______________________________
Mobile No: ________________________________________________________________________________________ DOS Membership no: ___________________
Email ID: _______________________________________________________________________________________Signature: ___________________________________

Email your answer to: [email protected]

www.dosonline.org/dos-times DOS Times - Volume 25, Number 1, July-August 2019 71

Tearsheet

Management of Superior Oblique
Palsy

Tear sheet
Dr. Gunjan Saluja MD, Dr. Swati Phuljhele Aalok MD

Management of Superior oblique palsy
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

Gunjan Saluja, MD, Swati Phuljhele Aalok MD

Vertical Diplopia

Park’s three step test (Maximum hypertropia on
contralateral head tilt

Head posture in previous childhood pictures

Absent Present

Small Vertical Large Vertical High Vertical Fusional
Fusional Fusional Vergence
Vergence Vergence
Congenital
Acquired Congenital Superior Superior oblique
Superior oblique Palsy
oblique Palsy Palsy

Management by
Knapp’s classification

Age<40 years Age >40 years

Imaging to rule out Risk factors of
space occupying mono-neuropathy
lesion

Present Absent
Observe Imaging

72 DOS Times - Volume 25, Number 1, July - August 2019 www.dosonline.org/dos-times

Tear sheet Tearsheet

Hypertropia worse on Right inferior oblique
adduction and upgaze weakening

Hypertropia worse on Right Superior oblique
adduction and downgaze strengthening (tuck)
If tendon is lax

Hypertropia worse on Right inferior oblique
adduction recession , if RHT< 25 PD,
Tuck Superior oblique, with
Hypertropia worse on Inferior oblique recession, if
adduction and downgaze RHT>25 PD

1ST procedure, Tuck R
Superior oblique, with
Inferior oblique weakening,
2nd procedure, left Inferior
Rectus recession

Hypertropia worse on all Tuck right superior oblique,
downgaze positions or
weaken left inferior rectus

Bilateral superior oblique palsy Bilateral Superior Oblique
Traumatic palsy, Brown’s plus syndrome tuck
Explore trochlea

Knapp’s classification for right superior oblique palsy*1

Corresponding author Corresponding Author:
Gunjan Saluja, MD, DNB, FICO
[email protected] Dr. Gunjan Saluja MD
Senior Resident, Dr. Rajendra Prasad Centre for Ophthalmic
Squint,Neuro-ophthalmology and Oculoplasty Services Sciences, All India Institute of Medical Sciences,
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India.
AIIMS, New Delhi

1c

www.dosonline.org/dos-times DOS Times - Volume 25, Number 1, July-August 2019 73











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