DOS_Nov_2007

Contents

E7 ditorial Photo Essay

R9 emembrance 73 Congenital Midline Facial Swellings

Focus Madhu Karna

11 Dysfunctional Tear Syndrome I75 ndustry News

Cornea / Ocular Surface Disease A77 bstracts

19 Descemet’s Stripping Automated Endothelial Keratoplasty Clinical Monthly Meeting

Massimo Busin 81 Case 1 - Ophthalmoplegia-Looking Beyond the Obvious

25 Deep Anterior Lamellar Keratoplasty: Big Bubble Technique Sandeep Bhuttan, Suma Ganesh, Manish Sharma, Archana Gupta

Namrata Sharma, Jeewan S. Titiyal, Rasik B. Vajpayee 87 Case 2 - Bevacizumab (Avastin) in Management of

29 Automated Lamellar Therapeutic Keratoplasty Neovascular Glaucoma
Suneeta Dubey, M. Agarwal, Monica Gandhi,
Jeewan S. Titiyal, Namrata Sharma, Rasik B. Vajpayee Gourav Sood, A.P. Pandey, Julie Pegu

Refractive Surgery 91 Clinical Talk-Determining Progression of Glaucoma on Perimetry

33 Sub-Bowman’s Keratomileusis Gaurav Sood, Suneeta Dubey, Monica Gandhi, Julie Pegu

Stephen G. Slade, Daniel S. Durrie Columns

Retina 99 DOS Quiz

39 Central Serous Retinopathy Saurabh Sawhney, Ashima Agarwal

Bhuvan Chanana, Raj Vardhan Azad F102 orthcoming Events

Ocular Tumours M105 embership Form

45 Current Concepts in Retinoblastoma Tearsheet

Santosh G. Honavar 109 Intraocular Lens (IOL) Designs

Neurophthalmology Sanjay Ahuja, Rishi Mohan, Aditi Gupta

65 Analyzing Disc Edema

Rohit Saxena, Munish Dhawan

Delhi Ophthalmological Society Website

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6

Editorial

Component Surgery of Cornea

We have moved from a world of overkill therapeutics where the diseased corneal tissue was replaced either with a full thickness
graft (penetrating keratoplasty) or a partial thickness graft (lamellar keratoplasty). The corneal surgeons have cleverly taken
advantage of the layered structure of the cornea. For superficial corneal opacities there is an option of phototherapeutic
keratectomy; for corneal opacities involving upto mid stroma, automated lamellar therapeutic keratoplasty or a manual lamellar
keratoplasty can be done. Opacification of the cornea involving up to the posterior stroma and sparing the descemet’s membrane
are dealt with the technique of deep anterior lamellar keratoplasty which can be done either using Anwar’s big bubble technique
or Melles technique which nearly but not exactly and always reaches up to the Descemet’s membrane. In cases where the
endothelium is diseased, but the stromal layers are not involved Francis Price technique of Descemet’s Stripping endothelial
keratoplasty may be undertaken. In cases of corneo-iridic cars and leucomatous corneal opacities penetrating keratoplasty should
be done. These subset of patients contribute to quite a substantial number of our corneal pathologies unlike in the western
countries. The concept of component surgery of cornea is not only beneficial from the patient point of view but also for the
Eye Banks. One tissue may be used for several procedures and surgeries may be planned accordingly. However, strict quality
control should be observed in these cases.
At this point, we mourn the sudden and untimely demise of our dear friend Dr. G. Sitalakshmi a renowned corneal surgeon
from Sankara Nethralaya. She had a keen interest in the subjects of “Ocular Surface Disorders” and “Infectious Keratitis” and
was the pioneer of “Osteoodontokeratoprosthesis” in India. This is a huge loss to the community and to the entire ophthalmic
fraternity. On behalf of all the members of Delhi Ophthalmological Society we bid her farewell and pray that her family gathers
strength to face this.
It is ironical that she very recently contributed to the article on “Modified Osteoodontokeratoprosthesis” in the July issue of
DOS Times this year. Coincidentally this issue’s theme is Component surgery of Cornea. It is indeed ironical that we last met in
Frankfurt her parting words that I remember were, Life is too short. I want to do more and more of OOKPs as these are the
patients who no one wants to operate upon and so I am concentrating more on this surgery now. Life was indeed too
short for her …..
Namrata Sharma
Secretary,
Delhi Ophthalmological Society

7

8 DOS Times - Vol. 13, No.4, October 2007

Dr. G. Sitalakshmi Remembrance

Ajay Dave MS

Dr. G. Sitalakshmi, 48 years , ophthalmologist, researcher and personality who did outstan-
a dear colleague passed away recently after a brief illness, at dingly well with her patients and
Chennai. She is survived by her husband, Dr. Tarun Sharma colleagues, alike.
and son , Abhishek, who is currently studying in USA.
In a short span of her career, she Dr. G. Sitalakshmi
Dr. Sitalakshmi was working at Sankara Nethralaya for almost performed over 16000 cataract
16 years. She had done her Diploma in Ophthalmology from surgeries. Her effort in forwarding
Madras University and subsequently at Sankara Nethralaya. the work in Osteo-odontal
She completed her Fellowship training at Sankara Nethralaya Keratoprosthesis was crowned
and became a Consultant in the field of Cornea at the same with the inaugural of MOOKP
institution. She also met and married Dr. Tarun Sharma, a Centre at Sankara Nethralaya by
vitreo-retinal surgeon. Both complemented each other and Dr. G. Falicinelli.
brought their respective fields to global standards.
In her recognition of work in Eye Banking and Cornea
When I joined Sankara Nethralaya in 1989 as a Fellow & Donation, 8th September has been declared as 'Dr. G.
Consultant, I received an unstinted support from her. Cornea Sitalakshmi Day'
at that stage was fledgling and Eye Banking was yet to be
organised. Her unbridled enthusiasm and effort put Cornea at I am sad at the loss of a friend and colleague. On behalf of
an important level at the institution. She was a pleasant fraternity of Delhi Ophthalmological Society we extend our
heartfelt grief to Dr.Tarun Sharma and his family.

838/2, SFS Flats,
Saket, New Delhi-17

www.dosonline.org 9

Dysfunctional Tear Syndrome Focus

Madan Mohan Gobinda Mukherjee Ritu Arora MD Jeewan S. Titiyal MD Radhika Tandon
MS, FACS, FAMS DOMS, MD, FICS MD, DNB, FRCS (Ed),

FRCOpth

Dry eye syndrome or keratoconjunctivitis sicca is among the most common and problematic conditions reported to ophthalmologists
worldwide. 2007 International Dry Eye Work Shop -DEWS defined Dry eye as a multifactorial disease of the tears and ocular surface
that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface. It is
accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. The changing pathophysiology, diagnostic
paradigms, management pearls were discussed with eminent cornea specialists, the excerpts of which are being presented here.

Dr. Madan Mohan (MM), Chairman, M.M. Eye Tech, New Delhi. Dr. Gobinda Mukherjee (GM), Senior Consultant of Ophthalmology,
Mukherjee Eye Klinik, New Delhi. Dr. Ritu Arora (RA), Professor, Guru Nanak Eye Centre & Maulana Azad Medical College, New
Delhi. Dr. Jeewan Singh Titiyal (JST) Professor, Cornea & Refractive Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All
India Institute of Medical Sciences, New Delhi. Dr. Radhika Tandon (RT) Professor, Cornea & Refractive Services, Dr. Rajendra Prasad
Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi.

Dr. Noopur Gupta (NG) MS, DNB, Senior Research Associate (Pool Officer) at Cornea & Refractive Services, Rajendra Prasad Centre
forOphthalmic Sciences, All India Institute of Medical Sciences, New Delhi, interviewed them on the current status of Dry eye.

NG: What percentage of patients in your clinical practice I have encountered unusual presentations of dry eye eg.
present with dry eye? Have you come across any unusual when patients have presented with filamentary keratitis or
presentations of dry eye? silent inferior corneal perforations due to dry eye or just
presented with microbial keratitis. I have also seen patients
MM: Primary dry eye disease in my practice is about 5-10%. with peripheral cataract wound melts where the surgeon
Another 15-20% of my patients present with symptoms had missed the dry eye and patient was also receiving topical
suggestive of dry eyes, which either coexist with other ocular diclofenac or topical ketorolac and patients in the post
pathologies or are secondary to other ocular diseases or operative period.
due to local or systemic medication.
Unusual presentations - Yes. Some patients can present JST: It all depends on the type of institution or practice one is in.
with watering as a complaint, which is paradoxical, since I see more of cornea and cataract patients. In my clinical
they have underlying dry eye disease. practice, dry eye patients make up around 10% of all cases.
Most of them are middle-aged and older, while some
GM: In my clinical practice I see about 14-18 % cases of mild to patients are young specially those with associated allergic
moderate dry eye, and about 3-4 % of severe dry eyes. Out disease.
of these 60 -65 % cases are females over the age of 45 years.
I have noticed an increasing incidence of dry eye in the RT: I predominantly get referral cases related to cornea and
younger age group patients with long working hours, external diseases of the eye. Dry eye forms a large
associated with prolonged use of computers in air- proportion of the disease pathologies. Approximately 40%
conditioned environment. There are some patients, who cases have dry eye of varying degrees.
along with dry eye, may often present with recurrent
corneal erosions, pterygium and Salzman’s nodular NG: What percentage of patients have dry eye secondary to
degeneration. local ocular pathology like concomitant meibomianitis,
blepharitis or allergic disease? Does a significant number
RA: I encounter 20-30% of my patients with mild to moderate of your dry eye patients have an associated systemic
dry eye usually related to prolonged working in front of disease?
computers, associated with allergic findings. As I am also
working with HIV patients, the incidence of concomitant MM: About 30% of patients have aqueous tear deficiency due to
dry eye is higher in them perse because of disease or due local ocular pathology; 4-5% are associated with
to Anti Retroviral Therapy. rheumatoid arthritis and other collagen disorders, atopy,
asthma etc. The rest two thirds are associated with

www.dosonline.org 11

Meibomian Gland Disease (MGD), chronic trachoma, Lissamine Green staining lid margin and tear meniscus
Blepharitis etc. height. To confirm the diagnosis and for monitoring, 3-4
of these tests are usually performed.
GM: Nearly 40-45% case of dry eye are secondary to
concomitant ocular diseases. Mebomian gland disease GM: Proper evaluation of symptoms and clinical examination
(MGD) perhaps is the major culprit in this group. A good of lid margin, tear meniscus, blinking reflex, overall
number of cases present with healed trachoma or with assessment of ocular surface and non invasive TBUT gives
sequeale of trachoma more so in the older age groups. the diagnosis. Primarily TBUT, Schirmers test (with and
5-7% cases of dry eye have associated systemic diseases with anesthetic), Fluorescein staining are my routine
like rheumatoid arthritis Stevens Johnsons Syndrome (SJS), investigations for Dry Eye cases. Additionally I may do the
Sjogrens Syndrome, Ocular Pemphigoid etc. Rose Bengal and Lissamine green staining tests if the need
arises.
Approximately half of the patients
(50%) have an identifiable local RA: My baseline investigations are Schirmer’s test, careful
evaluation of the tear film meniscus, tear film height, BUT
pathology (VKC, trachoma, and fluorescein staining. I have started depending more
meibomianitis, blepharitis, etc.) and more on the tear film meniscus and decrease in the
tear film height as the basic parameters in my practice,
Approximately 30% have an mainly because of the load of patients one has to evaluate
associated systemic disease and in the OPD but Schirmer’s test in unanasthetized corneas
gives reasonably clear diagnosis. Also corneal surface
20% are idiopathic should be evaluated carefully for any irregularity which
can be picked up by indirect or retroillumination method.
RA: Yes a large percentage of my patients have dry eye secondary
to local ocular pathology. Important being Vernal Kerato- JST: The first most important thing is clinical examination.
Conjunctivitis and other allergic eye disorders and Investigations are only needed to authenticate the diagnosis.
secondary to usage of topical antivirals and antiglaucoma The first test should be recording of visual acuity both for
medications. Post LASIK dry eye being commoner too. I distance and near. Then I will go for Non-invasive BUT, if
do see a lot of dry eye patients with chemical –chuna burns, possible. The tear meniscus and corneal staining may then
in children with vitamin A deficiency, post exanthematous be examined and subsequently followed by Schirmer's test.
fever etc. I also have large number of dry eye patients with Rose Bengal and Lissamine green staining may then be
associated RA or other collagen vascular disorders. Also 5- carried out if needed. The most reliable test in terms of
10% of my patients have typical sicca syndrome with therapeutic and diagnostic value can be diminished BUT
associated dry mouth. Oculomuco cutaneous syndromes and corneal staining.
also form a significant subgroup.
RT: I perform Schirmer’s test, Break up time and fluorescein
JST: Most patients presenting to us especially younger patients staining in all cases of dry eye. Other tests that I recommend
have an associated ocular pathology i.e. VKC, blepharitis are Lissamine green Rose Bengal staining and tear function
etc. The older patients have associated lid and/or Index.
meibomian dysfunction. Females above 45 years of age
may have associated systemic disease like rheumatoid Larger percentage of our patients
arthritis or menopausal hormonal disbalance. Other group
of patients who have infectious or inflammatory disorder have dry eye secondary
are also present.
to local ocular pathology
RT: Approximately half of the patients (50%) have an
identifiable local pathology (VKC, trachoma, NG: In which cases of dry eye do you carry out impression
meibomianitis, blepharitis, etc.) Approximately 30% have cytology?
an associated systemic disease and 20% are idiopathic.
MM: At our clinic, we do not perform impression cytology for
NG: What baseline investigations do you perform in a patient dry eye evaluation. The history, symptoms, clinical findings
of dry eye? Do you perform Schirmer’s test, phonel red & other tests are sufficient to diagnose and monitor the
thread test, tear pH, osmolality, Break up time (BUT), condition.
Fluorescein staining-all or any 2-3 tests. Which test do
you think is most reliable? Any other tests that you GM: To know the status of of the surface epithelium and goblet
recommend? cells, impression cytology is a good tool. But I feel this is
more academic and routinely I would not order for this.
MM: Schirmer's I/II are routinely performed. In addition we
check the tear pH, Tear Break up time, Fluorescein & RA: Only if there is some study or for confirmation of stem cell
disease.

JST: Basically, is cases where we suspect mucin deficient dry eye
or a decreased goblet cell count and in cases of limbal stem
cell deficiency.

12 DOS Times - Vol. 13, No.4, October 2007

RT: I carry out impression cytology in cases where limbal stem RT: If the frequency of tear substitute prescribed is less than 4

cell deficiency is suspected and limbal stem cell times a day, I use preserved formulations like polyvinyl

transplantation is planned. alcohol+povidone, and I use non-preserved preparations

NG: Do you use preserved or non-preserved tear substitutes- like carboxymethyl cellulose if the frequency is more than
which class of tear substitute (HPMC, PVA+Povidone, 6 times per day.
CMC, Na Hyaluronate) do you prefer? Any specific class In mucin –deficient dry eye, I use povidone.

of tear substitute for a specific disease? NG: Any role of electrolyte supplementation in artificial tears?

MM: Routinely I prefer to use transiently preserved tear MM: The presence of essential electrolytes in the tear substitute
substitutes. In some instances, to keep down the cost of definitely gives better results. The preparation however,
treatment, I do advise tear substitute with preservatives should not be hyperosmotic.
particularly when frequency of instillation is less than 3-4
times a day. GM: Electrolyte supplementation in tear substitutes definitely
In such cases where the tear substitutes have to be used have a role in maintaining the stability of the ocular surface.
more frequently, and those who are on multiple drug Electrolytes take care of the osmotic balance of the surface
epithelial cells and thereby add to the therapeutic value of
Non preserved tear substitutes are artificial tears.
preferred to reduce the epitheliotoxic
effects of the preservatives. Cost and RA: Can’t say but of late, role of compatible solutes in the form
maintenance are the limiting factors of glycerin, certain AAs and Glycols is being talked about
as osmoprotective agents and better than hypotonic agents
therapy, for other local eye diseases, I prefer to prescribe in maintaining the health of corneal epithelial cells thus
non-preserved tear substitutes. reducing the release of pro -inflammatory agents.
In mild cases, I start with HPMC or CMC as my first choice.
For moderate dry eye cases, I prescribe PVA- Povidone JST: It is again a debatable issue. It may not work in all patients
and CMC, to be used alternately. I give Na-Hyaluronate as unless the patient has increased osmolality of the tears.
additional therapy in moderate to severe eye cases. Usually, it does not last that long , so the benefit is not as
I prefer the substituted - Cellulose ethers (HPMC, CMC) expected. In fact we should have a tear substitute which
for primary dry eye conditions. should act at the cellular level and corrects the osmotic
imbalance at that level.
GM: I would advice tear substitutes without preservatives in
case the patient is either going to use the drops more than RT: I am not aware of any well documented clinical evidence so
four times a day or if the patient has been using the tear far. I do not think there is any specific role and would reserve
drops for more than 6 months. Apart from this all cases my opinion in this issue till a properly designed randomized,
with compromised stem cell and corneal epithelium controlled trial is performed.
problems should be using preservative free tear substitutes.
In mild to moderate dry eyes I tend to suggest PVA along NG: Do you use cyclosporine eyedrops in dry eye-if yes, what
with Povidone or CMC. But in Severe dry eyes I resort to is the indication and which patient is a suitable candidate?
CMC or Sodium Hyaluronate. What is the concentration and frequency of cyclosporine
drops you use? Which type of preparation (aqueous or
oil based) do you prefer ?

MM: I prescribe cyclosporin eye drops, in select cases of moderate
to severe dry eye conditions. I try to assess whether the
patient will be able to afford it for prolonged use. I use

RA: I prefer non preserved tear substitutes to reduce the 0.05% cyclosporine is indicated when
epitheliotoxic effects of the preservatives. Cost and associated with chronic inflammatory
maintenance are the limiting factors. I commonly use topical
CMC or HPMC. Prefer sod. hyaluronate only in severe component or ongoing immune
dry eyes to reduce the frequency of use of conventional inflammation e.g. severe VKC, some
tear substitutes. I also use gel preparations commonly as cases of autoimmune diseases related to
they spread uniformly over the ocular surface thus reducing dry eye and Steven Johnson syndrome.
the need for tear drops to be used frequently.
HPMC in the gel form for all my post corneal transplant
patients.

JST: I normally prefer non- preserved tear substitutes if the cyclosporin 0.05% in aqueous base, twice daily to start and
patient can afford. Otherwise, I use artificial tears which taper it only after 6 months to 1 year.
are transiently preserved. If there is aqueous deficiency,

then HPMC or CMC may be used. In cases of decreased GM: Yes, I use topical cyclosporine as a 0.05% aqueous base
BUT, I'll prefer CMC because of longer retention time. I
formulations for cases of moderate to severe dry eye. In
prefer sodium hyaluronate in contact lens related dry eye.
addition I would not hesitate to add cyclosporine at any

www.dosonline.org 13

stage of dry eye if there is any element of ocular surface side effects noted by patients are those of ocular burning.

inflammation. JST: Normally it takes 4-8 weeks to take effect. There are only

RA: Yes I do use topical cyclsporine eye drops in certain cases of minor side effects seen with cyclosporine drops like stinging,

dry eyes. Use in moderate cases of dry eyes has lead to burning and redness noticed in some patients. There have

decrease in the frequency of use of tear substitutes. I have been no major adverse effects noted by us with the routinely

found them very useful in patients with dry eyes with used concentration of the drug. The burning sensation

immunological problems esp. associated RA. Cases with disappears within few days of use and can be overcome

inflammatory origin of dry eyes do best with topical .05% with artificial tears. .

CsA in bid dose. Am not sure of its role in post LASIK dry RT: A significant response is only expected when the drug is
eye, though have encountered the prescription from instilled for at least 3 months. Steroids are used in
refractive surgeons. I prefer aqueous base CsA because of conjunction only if active inflammation is present as in
less stinging though cost factor is important. VKC. The adverse events to look out for are irritation,

JST: We do use cyclosporine in many of our dry eye patients burning, stinging and secondary infection.

when they have an associated inflammatory component. NG: How do you taper or stop cyclosporine drops in your
We normally start with available commercial preparation patients-whether stopped totally or not?
i.e. 0.05% twice a day (aqueous based). Since the response

does not start immediately, surface acting steroids to control MM: Cyclosporin once started needs to be continued for many
the inflammation may need to be added.
years and at best it may be possible to reduce the frequency
In patients with chronic inflammation and allergy e.g. SJS ,
to once a day. Its total stoppage may revert the condition to
1-2% cyclosporine drops in aqueous base or dissolved in
the original state.
artificial tears may be used.
GM: After evaluation if there is a improvement in the dry eye
RT: Yes. 0.05% cyclosporine is indicated when associated with
status and ocular surface condition, I would consider
chronic inflammatory component or ongoing immune
tapering off topical cyclosporine, after 4 to 6 months.
inflammation e.g. severe VKC, some cases of autoimmune
diseases related to dry eye and Steven Johnson syndrome. RA: I usually stop cyclosporine drops 6-8 months after initiation
of the therapy. Also these patients may be receiving
Oil based formulation available is expensive and if the price
concomitant systemic steroids for the associated systemic
is not an issue, oil- based formulation is better in cases of
conditions which then take over.
dry eye.

NG: When do you expect a significant response with JST: The minimum duration of cyclosporine therapy in any case
of inflammatory dry eye who is tolerant to therapy is 4-6
cyclosporine (CsA) drops-do you use steroids in
months. The patients' response is then adjudged and the
conjunction? Any adverse events to watch out for!
drug may be continued for another 6 months. On
MM: It takes 4-8 weeks for cyclosporine drops to offer a significant completion of therapy, it need not be tapered and may be
relief. I do use diluted steroids and other surface acting stopped immediately.
mild steroids such as fluorometholone and keep these RT:
patients under close observation for any increase in IOP or I stop the cyclosporine drops 6-12 months after use or
increase in ocular surface staining. sooner if the patient is intolerant to them. I do not taper
them.
GM: I have noticed the onset of the beneficial effect of topical
cyclosporine between 3 to 6 weeks of initiation of treatment. NG: What is the compliance and response of the patients to
cyclosporine drops?
In case of ocular surface inflammation I prefer to add topical

fluromethalone, three to four times a day, which I gradually MM: Affordability of this mode of therapy is of vital
taper off in 3 to 4 weeks. consideration. The Indian preparation
costs the patients roughly Rs. 5/- per day
Except burning and irritation in in comparison to imported drug, which
is 4-5 times more expensive. The long
some patients, I have not had Significant response with CsA term compliance of this treatment is
any other problems with topical very vital and it needs to be stressed,
cyclosporine therapy. is not observed before 6

RA: Significant response is not weeks of the institution of since patients often stop treatment or
switch over to other modalities, after a
observed before 6 weeks of the therapy. Proper counselling of few months, due to high cost of
institution of therapy. Proper the patient is needed
counselling of the patients treatment.

started on topical CsA is

essential to expect the GM: About 80–85 % tolerate the drug pretty well, and after 3 to

improvement in dry eye state only some time later in the 6 weeks of therapy most of the patients are symptomatically

course of treatment. I sometimes add topical diluted much better off.

steroids in symptomatic cases in the early period of the

initiation of topical CsA to reduce the symptoms like RA: Compliance is usually good, if counselled well for the

stinging and irritation arising from inflammation. Major stinging sensation. BID dose instillation is also convenient.

14 DOS Times - Vol. 13, No.4, October 2007

Cost is the major hitch. Usually these patients also receive GM: In dry eyes associated with systemic diseases, the relief of

concomitant tear substitutes. It is important to gauge the symptom is often delayed, more so if the underlying

expectation of patient and work accordingly. They are of systemic condition if not taken care of. These are the

little value in severe dry eye patients. patients I would refer to an internist for management of

JST: It all depends on proper case selection. If case selection is their systemic condition, after starting them on topical
appropriate, then compliance and response is good. drops.

RT: I have often experienced that economic considerations do RA: Yes, dry eye associated with systemic disease responds

drive the patients to request a switch from a more differently from that without any systemic disorder. Those

expensive brand to a with associated systemic disorders sometimes improve once

cheaper substitute. This put on systemic steroids or
must be interpreted in
Generally surface acting topical steroids immunosuppresants. There
may be decrease in the need for
the context of a large like fluoromethalone are used 4-6 times
government hospital a day for 1-2 weeks and then tapered. At topical tear substitutes. I also add
practice and may not systemic Pilocarpine 5mg tds in
some of my patients to increase
be generalized to more
affluent sectors of the the outset, a warning and counseling the tear secretion. Caution them
society. regarding the potential harmful effects for diarrhoea or sweating arising
out of this treatment. Some

NG: Do you prescribe like glaucoma and infection patients do tolerate this form of
topical steroids to your therapy also. Not to be used for
patients-if yes, how dry eye associated with SJS.

frequently and indications? JST: As far as dry eye in relation to local ocular pathology is

MM: Fluorometholone drops 2-3 times daily to start with is my concerned, presentation is early and treatment is simpler.

drug of choice for the treatment of severe dry eye disease In patients with associated systemic disease, presentation

particularly when dry eyes are associated with allergic is usually late and more severe. They may present with

disease or moderate to severe inflammation. peripheral corneal thinning without any preliminary

GM: In case of ocular surface inflammation I prefer to add topical symptoms of dry eye. Management of these cases is related
to control of the systemic disease alongwith local support.
flurome-thalone, three to four times a day, which I RT:
Peripheral corneal involvement is more common in
gradually taper off in 3 to 4 weeks. systemic disease. It is usually non-responsive to
conventional therapy and may require to systemic
RA: I do add topical loteprednelol in some of my immune immuno-supression.
mediated dry eyes or in patients not able to afford
cyclosporine eye drops. I use them in qid dosage for short
term use to suppress an acute flare up of the surface NG: Do you use punctal plugs/cautery-if yes, indications?

inflammation. Caution to be used when proposed for long MM: Yes, in moderate degree of dry eye disease, when patients
term use, for cataracts, glaucoma, peripheral corneal needs tear substitute more than 4-5times a day. Punctal
thinning etc. plugs are very helpful in these cases.

JST: Yes, we do prescribe topical steroids in dry eye patients GM: I would advice punctual occlusion in all cases of severe dry
with associated conjunctival and/or corneal inflammatory
eyes, and in some moderate dry eye states. Initially I would
component. They are used in conjunction with artificial
use temporary punctal plugs, and then finally after the
tears with frequent follow-ups to watch out for ocular
patient is convinced and feels better I would use a permanent
complications of topical steroids. They are usually
punctual plug. I do not advocate punctal cautery.
prescribed for a short duration until some other anti-

inflammatory agent takes over. RA: I use punctal plugs in moderate dry eye patients. Always

RT: Sometimes in VKC. Generally surface acting topical steroids try temporary collagen plugs before permanent ones.
like fluoromethalone are used 4-6 times a day for 1-2 weeks Sometimes dry eye worsens after the use of punctal plugs
and then tapered. At the outset, a warning and counseling because of the collection of tears with all the inflammatory
regarding the potential harmful effects like glaucoma and agents making the symptoms worse esp. in cases with
infection. inflammatory dry eye.

NG: Do you think that dry eye associated with and without JST: We do use punctal plugs quite often, especially in

systemic disease presents or responds differently? evaporative variety of dry eye or when there is aqueous

deficiency. Collagen plugs are first tried to assess the

MM: Yes, dry eye associated with and without systemic disease patient's response and if successful, permanent punctal
presents and responds differently. There is often corneal plugs are inserted in the inferior puncta.

involvement and associated dryness of the mouth etc. Dry RT: If puncta are open and patient is refractory to maximal
eyes associated with systemic diseases are slow to show tear supplementation, then plugs may be applied and
improvement and symptomatic relief. follow-up with cautery, if needed.

www.dosonline.org 15

NG: Do you use autologous serum-yes or no? RA: I do prescribe oral omega 3 fatty acids but easy availability
in the market is not there. I do encourage the patients to
MM: Autologous serum - I don't use it any more. consume fish products.

GM: I have no personal experience of using autologous serum JST: Not in any of my patients till date.
drops.
RT: Not yet.
RA: Only as an adjunct in nonhealing epithelial disorders
associated with dry eye as topical 20%serum drops improve NG: What is the future of dry eye therapy and diagnosis?
the health of corneal epithelium. I have not used topical
MM: We need to find good tear stimulants, at the same time
We need to find good tear continue our search for better tear substitute with lasting
stimulants, at the same time effect. A lot of hope is there on androgens, evaporation
continue our search for better retardants and newer polymers.
tear substitute with lasting effect.
GM: (i) Better diagnostic techniques which can access the
A lot of hope is there specific flaw in the tear film and ocular surface.
on androgens, evaporation
retardants and newer polymers (ii) Further understanding of the path-mechanisms of
dry eye condition.

(iii) Availability of tear substitutes which can specifically
replace or supplement the deficient layer.

(iv) Availability of drugs like Omega 6 fatty acids and PGE-
I (tear specific anti inflammatory prostaglandin)

RA: Future of dry eye therapy:

serum drops in isolation for the treatment of dry eye. Development of P2Y2 receptor agonist to increase aqueous

Caution for infection is a must when using these drops. I tear volume and stimulate mucin secretion, Androgen/

have used them for peripheral thinning disorders with estrogen supplementation, nutritional support,

equivocal results. Can be tried when other modalities fail osmoprotective tears, tears with polymer like HP guar to

in the management of dry eyes. reinforce the structural integrity of the ocular surface

JST: To be very frank, I have not used autologous serum. There environment. Development of secretagouges may be

have been some studies in our centre to evaluate the helpful.

efficacy of autologous serum in severe cases of dry eye. JST: The future of dry eye will involve 2-3 aspects:
(i) Education of public regarding injudicious use of
The preparation and maintenance of serum is difficult.
systemic and topical medications.
But in some desperate cases e.g. Steven Johnson's
(ii) Education of dry eye patients
syndrome (SJS), its use might be considered.
(iii) Availability of a medication which will give prolonged
RT: Occasionally. I use autologous serum only in cases of
and long-lasting effect or a device with sustained
persistent epithelial defect not responsive to conventional
release of artificial tears e.g. inserts.
therapy.
(iv) In severe cases like SJS where the ocular surface is

NG: Do you prescribe oral Omega-3 fatty acids for dry eye? damaged, some long-lasting technology which could
rejuvenate or regenerate the ocular surface is

MM: Yes. I use them for chronic cases only. These are good foreseen.

adjuncts to other treatments. RT: Future will be tear inserts, omega -3 fatty acids, and

GM: Yes I have used oral Omega 3 fatty acids therapy in dry eye secretagogues like rebamipide.

patients. I feel these patient on oral Omega 3 fatty acids

symptomatically tend to do better than others.

DOS Correspondent
Noopur Gupta MS, DNB

16 DOS Times - Vol. 13, No.4, October 2007

Descemet’s Stripping Automated Cornea
Endothelial Keratoplasty

Massimo Busin MD1,2

DSAEK derives itself from the continuous improvement of The tip of a 25 gauge needle mounted on a 2.5 cc empty syringe is
the initial endokeratoplasty procedure, which we introduced bent upwards (Figure 3) before it is introduced into the anterior
in 1996. This technique included peeling of the Descemet, chamber at the 12 o'clock position.
preparation of a donor lamella of deep stroma, Descemet and
endothelium; insertion of the graft into the anterior chamber Aqueous (about 0.2-0.4 cc) is aspirated and air is injected, filling up
through a clear-cornea tunnel; and fixation of the graft onto the the anterior chamber. The tip of the needle is used to cut through
bare posterior corneal surface by means of trans-corneal sutures the endothelium and Descemet membrane following the contour
(Figure 1). of the superficial mark (Figure 4).

Results in the rabbit model were not encouraging, as the Then the needle is retracted and an ordinary 25 gauge cannula is
postoperative course was complicated by frequent misplacement mounted on the syringe and re-inserted through the same puncture
of the donor lenticule and high endothelial cell loss, thus making site. The cannula is employed to sweep away Descemet and
the use of this technique in humans unreasonable (Figure 1, right endothelium, usually in a single piece (Figure 5).
part)
As it is blunt, damage to the posterior stromal bare surface is
In 1999 Melles demonstrated that corneal layers can adhere to avoided. Whenever air is lost through the entrance site of the
each other permanently with no need for sutures and contributed needle/cannula, the anterior chamber is reformed by injecting new
substantially to the development of new posterior lamellar air with the syringe. Performing the whole manoeuvre under air
keratoplasty techniques. However, Melles and other surgeons allows perfect visualization of Descemet membrane and
employed hand dissection for the preparation of both donor tissue endothelium and eliminates the need for any type of dye or, much
and recipient bed, and surfaces obtained with this type of dissection more importantly, for any viscoelastic substance in the anterior
create an interface with an the optical quality which is very rarely chamber. In fact, if the viscoelastic substance is removed
compatible with 20/20 vision. incompletely before insertion of the graft, it may reach the interface
space, preventing adhesion of the donor tissue to the stromal
More recently, Price and Gorovoy have substantially improved surface and causing the procedure to fail.
the optical quality of the interface by introducing the
microkeratome-assisted dissection of donor tissue. Excellent visual A clear-cornea tunnel, 1 mm in length and 5 mm in width is
results, comparable, if not superior to those of conventional prepared nasally (Figure 6). The dimensions of the tunnel are
penetrating keratoplasty (PK), have been reported by both authors. critical for the uneventful insertion of the graft into the anterior
Nonetheless, the same complications encountered with the original chamber. If the tunnel is too long the donor tissue may remain
endokeratoplasty procedure (graft displacement and, especially, partly trapped during insertion, while a too narrow tunnel may
endothelial cell loss up to 40-50% one year after surgery) still seem cause an increase in endothelial cell loss through pronounced
to complicate the postoperative course of DSAEK in a relatively deformation of the graft.
high number of patients.
After coating the endothelial side with viscoelastic substance, the
The modified surgical technique presented below was developed donor cornea is mounted on the artificial anterior chamber of the
with the purpose of eliminating the major draw-backs of the ALTK system and most of the anterior stroma is removed by
present DSAEK technique, while retaining the major advantages means of the microkeratome with a 300 micron head, which usually
of a relatively simple, reproducible and safe procedure. Results cuts lamellae with a thickness between 350 and 400 micron (Figure
obtained 1 year after DSAEK surgery modified according to the 7).
technique presented below have shown that endothelial cell loss is
comparable to that recorded after conventional PK. The same marker used to mark the corneal surface is employed to
mark the stromal side of the remaining tissue (usually with a
Surgical Technique thickness between 100 and 200 micron), which is then punched to
the desired size (8 to 9 mm) (Figure 8).
A marker, usually 9 mm in diameter, is used at the beginning of the
procedure to outline the limit of the internal surface, from which As opposed to what is done by most surgeons, the donor tissue is
the endothelium will be peeled off (Figure 2). not folded and inserted into the anterior chamber with the so-
called "taco" technique. Instead, a specially designed glide is loaded
1. "Villa Serena" Hospital, Department of Ophthalmology, Forlì, Italy with the donor lamella, endothelial side up and crocodile vitreous
2. University of "Magna Graecia", forceps are used to grasp the donor button and pull it into the
glide opening (Figure 9).

A side entry is created temporally. The glide is then inverted and
positioned at the entrance of the nasal clear corneal tunnel. The

www.dosonline.org 19

Figure 1. Schematic (left part) and rabbit pictures (right part)
of the original design of endokeratoplasty

Figure 2. Circular mark, 9.0 mm in Figure 4. Descemetorhexis performed
diameter, outlining the extension under air bubble, using
of Descemet stripping. a 25 Gauge needle

Figure 3. 25 G needle bent both Figure 5. Blunt 25 G cannula used to remove
proximally and at its tip used to in a single piece Descemet membrane and
endothelium under air bubble
perform Descemetorhexis.
DOS Times - Vol. 13, No.4, October 2007
20

Figure 6. Clear-cornea nasal tunnel prepared Figure 9. The donor tissue is
with a keratome. pulled into the glide
opening by means of

crocodile vitreous forceps

Figure 7. Microkeratome assisted removal of the Figure 10. Insertion of the graft into the anterior
anterior stroma from the donor cornea mounted chamber with the "pull through" technique, using

on the artificial anterior chamber vitreous forceps and tissue glide.

Figure 8. Donor cornea mounted in the artificial Figure 11. Air is injected into
anterior chamber after microkeratome-assisted the anterior chamber
removall of the anterior stroma (using the 300 µm through a side entry to
head). The area to be punched out is marked attach the donor
tissue to the posterior
within the area of stromal removal and an corneal surface.
additional mark is made peripherally to identify
21
the stromal and endothelial sides.

www.dosonline.org

crocodile forceps are inserted through the side entry and passed An iridectomy is performed, if not already present, in order to
across the anterior chamber, exiting through the clear-cornea prevent papillary block and Urrets-Zavalia syndrome, secondary
tunnel to grab the graft and drag it into the anterior chamber to filling of the anterior chamber with air at the end of surgery.
(Figure 10).
The graft is finally attached to the posterior stromal surface by
The donor lamella is allowed to unfold spontaneously under means of air (Figure 11).
continuous irrigation .Gentle tapping at the inferior limbus may
facilitate centring of the graft. The whole manoeuvre is performed Both the clear-cornea tunnel and the side entry are sutured water-
with the aid of continuous irrigation with an anterior chamber tight with 10-0 nylon stitches. Triamcinolone acetonide and
maintainer inserted at the limbus at the 12 o'clock position. gentamicin are injected subconjunctivally at the end of the
procedure. The eye is patched and the patient is required to lie on
his back for the next 6-8 hours.

Author
Massimo Busin MD

Required

A Research Officer for the ICMR Project Entitled "Evaluation of Cyclosporin in Control of Ocular Inflammation
in Acute Steven Johnson's Syndrome" under Dr. Namrata Sharma for Three Years.
Applications with Detailed Curriculum Vitae and copies of Degrees/Certificates may be submitted by 20th October,
2007 in the office of Dr. Namrata Sharma, Room No. 474, 4th Floor, Dr. R.P. Centre for Ophthalmic Sciences, All
India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029

22 DOS Times - Vol. 13, No.4, October 2007

Deep Anterior Lamellar Keratoplasty: Cornea
Big Bubble Technique

1Namrata Sharma MD, 1Jeewan S. Titiyal MD, 2Rasik B Vajpayee, MS, FRCSEd, FRANZCO

The surgical considerations for DALK technique will be Descemet’s membrane removal
discussed under anesthesia, instrumentation and the surgical
technique. The Trypan blue dye is used to attain the membrane and this is
removed with the non-toothed forceps / Dry Merocel Sponge
Anesthesia
Suturing
We prefer to perform this technique under general anesthesia,
although other surgeons have undertaken this technique under Lims forceps / Pierce Hoskins forceps, Needle Holder and 10-0
peribulbar anesthesia. monofilament suture help in suturing the donor graft to the
recipient bed
In our experience, general anesthesia is preferable as this minimizes
intraoperative upthrust and hence prevents an inadvertent Surgical Technique
descemet’s membrane tear which may occur due to suboptimal
akinesia which occurs when the patient is given local anesthesia. Informed consent should be obtained from all patients.

Instrumentation The criteria for quality of donor tissue are not very stringent and
a donor cornea with suboptimal quality may be used to perform
The following instruments are required for DALK surgery. the lamellar graft. However, an optical quality donor corneal tissue
should always be kept in reserve in the event of a perforation
Exposure of palpebral aperture when DALK may have to be converted to a penetrating
keratoplasty. The steps of the surgical technique include the
A lid speculum should be used to expose the palpebral aperture. recipient dissection, donor preparation and graft host apposition.

Trephination Recipient Dissection

A caliberated guided trephine system (Krumeich, Rhein Medical) A superior and inferior recti bridle sutures are applied.
which can be set to any depth is preferred . The Hanna suction
trephine (Moria) is also accurate but can be set to 100 microns A Hessburg Barron (JedMed Instrument Co, St Louis, Missouri,
steps only. The Hessburg-Barron vacuum trephine is less precise USA) suction trephine (7.00 mm to 7.5 mm) is used for partial-
but is disposable and can be used easily. thickness trephination of the host cornea up to an approximate
depth of 300 microns depth or 60 to 80% of the pre-operative
Big bubble Injection corneal thickness. (Figure 1).

A 27- or 30- gauge needle attached to a 3mL to 5mL syringe which A 27-gauge disposable needle attached to a 5-ml syringe, bent at
is bent approximately 5.0mm from its tip so that the terminal 60 degrees, bevel down , is advanced in the paracentral stroma,
segment angles up approximately 60 degrees. and air is injected into the corneal stromal tissue, which forms a
large air bubble between the descemet’s membrane and the host’s
Side port creation

A MVR blade can be used to create the side port or paracentesis.

Anterior Keratectomy/Corneal debulking

A crescent blade 2.25 mm ( Alcon, Fortworth, Texas ) or a #69
Beaver blade ( Becton Dickinson Co. &) .

Penetration of anterior stromal layers

A30 degree ophthalmic knife (Alcon, Fortworth, Texas) or a blade
braker.

Quadrantic Splitting of anterior stromal layers

Quadrantic splitting of the anterior stromal layers can be done
with the helps of a blunted microscissors or Vannas scissors.

1. Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Figure 1. Partial thickness trephination of the host
All India Institute of Medical Sciences, New Delhi
2. Centre for Eye Research Australia 25
Department of Ophthalmology
University of Melbourne

32, Gisborne Street, East Melbourne, Victoria 3002, Australia

www.dosonline.org

Figure 2. Formation of Big Bubble by Air Injection Figure 3. Anterior debulking after air injection

Figure 4. Removal of residual stroma Figure 5. Suturing the donor cornea to the host

corneal stroma (Figure 2). The needle is advanced to about 2 to 3 A curved Vannas scissors is then inserted inside and a nick is given
mm in a plane almost parallel to the corneal surface so as to avoid on the stromal layers.Visocoelastic is then instilled again and this
perforation of the descemet’ s membrane. Subsequently, debulking nick is extended distally as well as proximally which divides the
of the anterior two-thirds of the superficial corneal stroma is stromal layers into two hemi-sections. A cut is also made towards
performed using a crescent blade (Alcon Surgical, Fort Worth, the nasal and the temporal side of this vertical incision so that the
Texas, USA) leaving a very thin layer of corneal stromal tissue overlying stromal layers are divided into four quadrants and each
over the large air bubble (Figure 3). quadrant is then excised baring the decemet’s membrane
completely ( Figure 4). Caution is required while giving nicks in the
A paracentesis is then created using a 15-degree blade (Alcon stromal tissue and this should preferably be done under the
Surgical) at the 10-o’clock position to lower the intraocular pressure viscoelastic cushion, taking care that the pressure is applied upwards
of the eye so that the descemet’s membrane falls posteriorly. A towards the stromal layers and not downwards towards the
small opening is created in the stromal tissue overlying the air descemet’s membrane .
bubble using a 15-degree blade (Alcon Surgical). This site of this
incision is marked with the help of a marking pen /genitan violet While removing these quadrants from the trephinated edges, a
stained sinskey hook prior to making an actual nick in the stromal posterior ledge usually forms all around circumferentially which
layers. This mark helps to identify the exact site of incision which occurs inadvertently as the surgeon avoids going very close to the
may get obscured due to the inadequately split stromal fibres . descemet’s membrane.
Following egression of the air bubble from the incision site, 2%
hydroxypropyl methylcellulose (Visilon, Shah & Shah, Mumbai, Donor Preparation
India) is injected through the opening to maintain the space between
the overlying corneal stromal tissue and the descemet’s membrane. Full-thickness donor corneal tissue stored in McCarey-Kaufman
medium may be used for transplantation. Circular trephine blades
(Storz Ophthalmics, St Louis, Missouri, USA) ranging from 7.5

26 DOS Times - Vol. 13, No.4, October 2007

Follow –up visits

Patients are followed up just as in conventional lamellar
keratoplasty. Follow-up visits are scheduled at 1, 7, and 14 days
and then monthly for 12 months. Additional visits are scheduled
in cases of complications or problems.

Post operative Parameters

A record of the following parameters should be kept at each visit:

Visual Acuity

Uncorrected visual acuity (UCVA), best spectacle-corrected visual
acuity (BSCVA) and best corrected visual acuity (BCVA) should be
noted at each visit.

Contrast Sensitivity and glare

Figure 6. Final post-op picture Although it is not mandatory to do these investigations in all cases,
contrast sensitivity and glare acuity may be assessed, if such facilities
are available.

Slit Lamp Examination

mm to 8.00 mm in diameter are used to punch the donor lenticule A detailed slit lamp evaluation should be done at each follow-up.
from the endothelial side of the corneoscleral button. The The graft clarity, status of the graft host junction and anterior
Descemet membrane of the donor corneal button is scraped off chamber status should be noted at each visit. If there is any
after staining it with 0.06% trypan blue dye (Visiblue, Shah & Shah) evidence, of formation of double anterior chamber, remedial
using a Descemet stripper. Alternatively a dry merocel sponge measures should be taken immediately. Any suture related problem
may be used to separate the stained Descemet’s membrane. The such as a loose suture, broken suture or tight suture should be
descemet’s membrane comes out quiet easily. The posterior corneal removed and replaced in the early post-operative period.
surface was thoroughly irrigated with BSS.
Corneal Pachymetry
Graft Host Apposition
Ultrasonic corneal pachymetry may be done in these cases at 1, 3,
The host graft disparity should be 0.25 mm with donor graft being 6 and 12 months.
larger than the host. In cases of keratoconus same sized donor
may be used to decrease myopia. The donor lenticule is placed on Corneal Curvature
the recipient bed. Four cardinal sutures are passed first. The edge
of the needle is passed just above the circumferential posterior Videokeratography should be done in all cases to assess the amount
stromal ledge which was created previously. The posterior ledge of post-operative astigmatism.
acts as a guide and any inadvertent microperforation is avoided as
the edge of the needle is kept above this ledge (Figure 5). Rest of Specular Microscopy
the 14 interrupted sutures are then passed using 10-0 monofilament
nylon suture ( Figure 6). Specular microscopy may be undertaken in these cases at 1, 3, 6
and 12 months.
Alternatively, following the application of cardinal sutures a single
continuous suture may be applied. Suture Removal

Post Operative Evaluation and followup Selective suture removal should be performed for any suture-
related problems and for control of astigmatism from one month
Post-operative Evaluation and follow-up onwards.

Ostoperative follow up and evaluation includes the post-operative To control astigmatism interrupted sutures are removed gradually
regime as well as the investigations which may be required from the third to the sixth month, beginning with the tightest
routinely or in special cases. suture, revealed by tangential topography as a localized steepening.
The continuous may be generally removed after 5 to 6 months or
when it becomes loose.

Post-Operative Regime

Post-operatively the patients are given a regime similar to that of First Author
a conventional lamellar graft. Patients receive topical antibiotic Namrata Sharma MD
drops such as 0.3% ciprofloxacin hydrochloride four times a day,
topical corticosteroid drops such as 1% prednisolone acetate eye
drops four times day, and preservative-free artificial tears every
two hours for the first month, which were subsequently tapered
over the next six months.

www.dosonline.org 27

Automated Lamellar Therapeutic Keratoplasty Cornea

Jeewan S. Titiyal MD, Namrata Sharma MD, Rasik B Vajpayee, MS, FRCSEd, FRANZCO

Lamellar keratoplasty with an automated microkeratome is a (or 0.5 mm undersized) and thickness as the donor disc. Once the
recent modification of the manual lamellar keratoplasty. This disc is removed, the recipient bed is washed with balanced salt
technique uses a microkeratome to excise the pathological part of solution and dried with the sponge.
the host cornea upto a particular depth and later a healthy donor
cornea, which is also, cut using an automated microkeratome and Preparation of the Donor Lenticule
artificial chamber is sutured in its place. This new lamellar grafting
eliminates several disadvantages associated with conventional LK The donor lenticule may be obtained from a corneoscleral rim.
including difficult surgical manual technique. The automated micro The corneoscleral rim should be at least 4 mm wide as the frill of
keratome helps in achieving a regular, smooth recipient bed and the corneoscleral rim has to be positioned on the artificial anterior
optimal recipient graft opposition. chamber maintainer. The artificial anterior chamber consists of a
stainless steel structure with 3 screw type safety rings. The lower
Indications for Automated Lamellar Therapeutic ring sustains a metal device that covers the superficial sclera and
maintains a tight fit on the metal base of the chamber to avoid
Keratoplasty leakage. A second ring in an intermediate position approximates
The indications for automated therapeutic lamellar keratoplasty the chamber on the former structure to tighten the sclera from
(ALTK) include patients having diseases involving the anterior to above. A third ring located superiorily is adjusted to modify the
mid-stromal part of the cornea with normal endothelium including height of the microkeratome plate. This plate is a gearless track to
superficial dystrophies, keratoconus, superficial chemical bums,
posttraumatic scars, postinfections leucomas, trachoma, herpes
and postrefractive surgery corneal haze related to the cap
complications.

Contraindications for Automated Lamellar Therapeutic Figure 1. Automated Microkeratome
Keratoplasty
The contraindications for ALTK include patients with disorders of
lids including ectropion, entropion, trichiasis, lagophthalmos, dry
eye, keratoconjunctivitis sicca, severe blepharitis, uncontrolled
uveitis, glaucoma and dense cataract. Any posterior segment
pathology of the eye that may preclude attainment of good visual
acuity after ALTK, immunocompromized patients where wound
healing may be impaired, collagen vascular disorders and history
of abnormal wound healing, e.g. keloid formation are other
contraindications of ALTK.

Preoperative Evaluation

The preoperative evaluation of a patient undergoing AUK is similar
to that of a routine manually dissected lamellar keratoplasty.
Pachymetry is of special relevance as the depth of the dissection is
dictated by the depth of the pathology as well as the micro keratome
head available.

Surgical Technique

Preparation of the Recipient Bed

The recipient lamellar bed is prepared using a suction ring and an
automated microkeratome in a manner just as one does in laser-
in-situ keratomileusis (Figure 1 & 2). The automated
microkeratome is used as a cutting instrument. The instrument
has a suction ring, which allows the surgeon to obtain a lenticule of
a specific size. It has various range of heads such as 120, 180, 250
and 350 mm which can used depending on the desired depth of
the lamellar cut. The goal is to cut a disc with the same diameter

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Figure 2. ALTK surgical trolley
All India Institute of Medical Sciences, New Delhi
29
www.dosonline.org

Figure 3a. Preoperative case of nebulomacular Figure 3b. Operated automated lamellar therapeutic
corneal opacity (Healed Keratitis) keratoplasty for patient as in Figure 3a

guide the micro keratome head translation at a constant height without any sutures, we prefer to put at least 8 interrupted sutures
along the corneal pass. with 10-0 monofilament nylon. The eye is than patched for 24
hours.
Depending on the height at which this plate is positioned, more
(lower position) or less (higher position) of the cornea is exposed, Postoperatively, the patient receives topical antibiotics, diluted
resulting in a larger or smaller lenticule diameter, respectively. The corticosteroids and artificial tears, which are then subsequently
chamber is connected to the infusion system with a reservoir of tapered.
saline solution, placed 1.2 m above the chamber level. An expansion
air chamber is located within the infusion line at the 10.0 cm of the Advantages
connection to the chamber.
An automated micro keratome allows the surgeon to obtain
We use LSK micro keratome (Moria) to perform automated corneallenticules with parallel faces that are almost identical in the
lamellar keratoplasty may be used to cut the corneas. It consists of donor and the recipient corneas. These factors result in optical
a single piece metal head connected to a nitrogen-gas-driven hand and refractive results that are better than those obtained with the
piece. The blade oscillates at a rate of 15000 oscillations / min with manual techniques. The cut made by the microkeratome is regular
an orientation of 25 degrees to the cut plane. The grooves on the and homogeneous. This prevents the irregular astigmatis that
base plate of the artificial anterior chamber are designed to fit into occurs, with a manual procedure because of the horizontal
the microkeratome head, hence its pass along the cornea is adherence of the disc to the donor tissue. Further, the surgical
uniform. time is shortened fewer sutures are required for shorter periods
of time, which reduces suture related complications.
To reduce the number of air bubbles beneath the cornea, rims are
placed on the chamber base after the infusion is released. Once There are several things surgeon should consider when using this
the cornea is stabilized and centered and the absence of air bubbles technique. It is important to obtain lenticules with same diameter
is confirmed, the infusion is closed, the superior metal support is and thickness so that the fit is perfect and the future epithelial in
placed and locked by turning the first ring clockwise, and the second growth is avoided. The epithelium of the donor should be kept
ring is turned anticlockwise to elevate the chamber height and intact as far as possible. The donor epithelium is replaced by the
tighten the scleral skirt between the support and chamber. recipient epithelium during the first week.

The applanation lens is then placed on the cornea to determine Outcome of ALTK
the plate height for the desired diameter, turning the second ring
counter clockwise or clockwise depending on the guiding circle Out of a total of 9 eyes that underwent ALTK at our center, 5
marks on the lenses,. Drops of saline solution are placed on the patients had nebulomacular corneal opacity (superficial corneal
cornea and keratectomy is performed by passing the scars), (Figure 3a) 3 had Salzmann nodular degeneration, and one
microkeratome head with its oscillating bade at a relatively constant had keratoconus. Five patients were males and 4 were females,
speed along the plate. Behrens et al report that the precision and with age ranging from 5 years to 65 years. The donor button size
accuracy of this system varies according to the attempted thickness ranged from 8.5 mm to 10 mm (thickness 350 mm) and the host
and diameter. Greater precision is obtained if the diameter of the cut size ranged from 8 mm to 9.5 mm (thickness 250 mm). Sixteen
cut is ~ 8 mm or if the flaps are thinner.2 to twenty four interrupted sutures with 10-0 monofilament were
applied (Figure 3b). The mean central corneal thickness was 503
Donor Recipient Apposition mm. From a preoperative visual acuity of <2/60 in all eyes, a
postoperative visual acuity of >6/24 was achieved in 8 out of 9
The donor lenticule is placed on the recipient bed. Although some patients. All grafts epithelized within first week of surgery. No
surgeons leave the donor lenticule adhered to the recipient bed cases of interface scarring were seen after a follow-up of 6 months.

30 DOS Times - Vol. 13, No.4, October 2007

However, the long-term problems of interface scarring needs to to penetrating keratoplasty especially in the treatment of anterior

be ascertained. corneal opacities.

Although we did not encounter any major complications, there References
are risks of postoperative complications, which include delays or
defects in epithelization, epithelial in growth in the interface, fibrosis 1. Jimenez-Alfaro I, Perez-Santonja J J, Telleria G G, Palcin B, Puy P.
and even vascularization. Edema or melting of the lenticule may Therapeutic lamellar keratoplasty with an automated microkeratome.
also occur. Although an endothelial rejection will not occur, an J Cataract Surg 27: 1161-1165, 2001.
epithelial and stromal rejection may occur. Finally the original
disease may recur. Optical lamellar keratoplasty, performed with 2. Behrens A, Dolorico AMT, Kara DT, Novick LH, McDonnell PJ,
an automated micro keratome, is an easy, simple, and accurate Chao LC, et al. Precision and accuracy of an artificial anterior chamber
technique. It produces good visual results and is a good alternative system in obtaining corneal lenticules for lamellar keratoplasty. J
Cataract Refract Surg 27: 1679-1687, 2001.

First Author
Jeewan S. Titiyal MD

Delhi Ophthalmological Society
Monthly Clinical Meeting, October 2007

Venue: Main Auditoriam, Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi-110002
Date and Time : 28th October, 2007 (Sunday), Clinical Session : 11.00 a.m. to 1.00 p.m.
Tea & Snacks : 10.30 a.m. to 11.00 a.m.

Clinical Cases: : Pankaj Vats 10 mins.
1. An unusual presentation of a common systemic disease P.K. Pandey

Discussion

2. Orbital SOL - How close are we to clinical diagnosis Discussion : Pooja Dhama 10 mins.
Sushil Kumar 15 mins.
Clinical Talk:
HIV and Ocular manifestations (Pre and Post HAART era) : Ritu Arora
GNEC-LNJP-MAMC experience

Symposium: Pediatric Teasers
Chairman: P.K. Pandey Co-Chairman: Sushil Kumar, J.L. Goyal

• Is age a bar to IOL implantation : Anju Rastogi 15 mins.
• Valves in childhood glaucoma : Usha Yadava 15 mins.
• Unusual presentation of common pediatric ocular tumors : Usha K. Raina 15 mins.

To be followed by Lunch

www.dosonline.org 31

Sub-Bowman’s Keratomileusis Refractive Surgery

Stephen G. Slade MD, Daniel S. Durrie MD

While laser in situ keratomileusis (LASIK) surgery has the surface, they have a significant advantage over mechanical-
advantages of superior visual results, efficiency and patient microkeratome flaps, which tend to have a more meniscus shape,
friendliness, the procedure can lead to dry eye, flap complications being thicker in the periphery and shallower in the center, resulting
and, arguably, an increased risk of corneal ectasia. The in less predictable flap thickness.
biomechanical stability of ablation at the outer surface of the cornea
in photorefractive keratectomy (PRK) resolves this issue; the The evolution of the femtosecond laser saw the introduction of
procedure leads to better correction of high-order aberrations the 60-kHz laser in 2006, which allowed the laser to create corneal
(HOAs), better quality of contrast sensitivity and night vision, and flaps about as quickly as the mechanical keratome, as well as
fewer complaints of dry eye. But the PRK procedure is more requiring less energy for flap creation and enabling closer
painful, particularly in the immediate post-operative period, and separation of spots and lines. The incidence of opaque bubble
has slower visual recovery, with increased risk of haze. In order to layers, which can form during the photodisruption process, is also
resolve this dilemma, LASIK and PRK can be combined to create reduced using the 60 kHz, which can make corneal flap-lifting an
one procedure that reaps the best of both; the visual recovery and easier task. Corneal flap creation using the femtosecond laser is
painlessness of LASIK and the safety and stability of PRK. This considered superior to flap creation using mechanical
new technique, sub-Bowman’s keratomileusis (SBK), involves the microkeratomes in various published studies.3,4,5
creation of a customized corneal flap that has a diameter based on
the requirements of the individual patient, in addition to the type Using the femtosecond laser to create corneal flaps means a lower
of excimer laser. standard deviation in the central thickness of the cornea and good
visual results in the early post-operative period. One of the first
Ectasia and other problems following LASIK procedures has comparative studies that evaluated results with the femtosecond
become an increasing concern, particularly following the laser versus results with a mechanical microkeratome concluded
biomechanical research on the procedure by Marshall, Alio and that flap thickness predictability was better achieved with the
others. Consequently many refractive surgeons are returning to femtosecond laser.6 Flaps of less than 150 µm can be created using
surface ablation techniques, which, although maintaining a mechanical microkeratome, but flap predictably becomes an
biomechanical stability, carry the disadvantages of pain, haze and issue. Kezirian and Stonecipher compared two mechanical
slower visual recovery. With regards to safety, surface ablation microkeratomes with the IntraLase Femtosecond Laser, showing
offers superior results in comparison to LASIK, but the visual that the mean flap thickness for the laser flaps was 114 ± 14 µm
results and patient satisfaction of PRK are not on par with those of (SD) with an intended thickness of 130 µm. With the Hansatome
LASIK. microkeratome, the mean flap thickness was 156 ± 29 µm with a
130 µm head, and with the CB microkeratome, the mean flap
Creating Customized Corneal Flaps thickness was 153 ± 26 µm, also with a 130 µm head.

The Femtosecond Laser vs. the Mechanical Microkeratome Recent biomechanical studies that compare the corneal response
to different types of laser refractive procedures suggest that corneal
The use of the femtosecond laser for LASIK has increased flaps created using a femtosecond laser are the most stable. The
substantially since it was first introduced in 2002. A market study study also proved that there was less surgically-induced astigmatism
has shown that approximately 30% of LASIK procedures were in the eyes treated with the femtosecond laser, and that there were
performed using a femtosecond laser by the end of 2006.1 fewer complications overall. In a prospective, contralateral eye
Literature suggests that the creation of a thinner flap (±100 µm), study comparing the femtosecond laser and the Hansatome
with a diameter based on the maximum ablation zone of the excimer Microkeratome, Durrie and Kezirian showed that uncorrected
laser, is more effective. To carry out customized flap creation, the visual acuity (UCVA) and manifest refractive outcomes were better
use of the femtosecond laser is crucial, as it is the only keratome with the femtosecond laser.7 Tran et al, studied induced aberrations
that allows surgeons to manipulate the flap depth, as well as flap following flap creation using the femtosecond laser and the
diameter. While the mechanical microkeratome creates corneal Hansatome, and concluded that HOAs increased significantly in
dissection using its metal blade, the femtosecond laser uses micro- microkeratome eyes, which was not the case for eyes treated with
photodisruption to achieve dissection, at a predetermined depth the femtosecond laser.8
using 1-mm pulses in either a raster or spiral pattern across the
surface, thus creating a flap that is almost completely planar.2 As Marshall et al, carried out a study on cadaver eyes, observing
femtosecond-laser flaps have an even thickness across the entire wound healing and corneal biomechanics following PRK, epi-
LASIK, mechanical microkeratome-assisted LASIK and
Slade & Baker Vision Center femtosecond laser-assisted LASIK. With the use of confocal
3900 Essex Lane, Suite 101 specular microscopy, electron microscopy, Shearing interferometry
Houston, TX 77027 and histology, the study concluded that the strongest part of the
cornea was the first 150 µm, and out in the periphery where the

www.dosonline.org 33

lamellae were packed tightly. Consequently, the corneas treated smaller flaps, patients who undergo the SBK procedure have less
with PRK, epi-LASIK and femtosecond laser-created flaps of ±100 dry eye and less inflammation, as they help to protect the lamellae
µm resulted in the greatest biomechanical stability and better in the periphery of the cornea. For surgeons, these flaps are easier
corneal transparency.9 to handle and position, with minimal striae or flap slips. SBK
enables the creation of a predictable, thin flap, quicker visual
Dupps and Wilson demonstrate that the interweaving of the recover, with minimal pain, and superior visual results, especially
lamellae provides a significant structural foundation for shear in the first 3 months. Post-operatively, the SBK procedure shows
(gliding) resistance, whereby the circumferential cutting of the reduced incidence of dry eye, minimal biomechanical changes with
central lamellae causes relaxation of the lamellae out in the fewer HOAs and a decrease in loss of corneal sensitivity.
periphery, leading to peripheral stromal thickening.10 The depth
of the lamellar cut is one of the most important factors in a LASIK SBK Methods
flap, and that corneal behavior is largely dependent on collagen
fibrin distribution.11,12 Out of the five layers of the cornea, Bowman’s With LASIK, flaps tend to be created as large as possible (9.5-10
layer and the stroma are the only layers that contain collagen mm) to compensate for any decentration. As the flap in the SBK
fibrils, which means that these layers have the most tensile procedure is smaller, it is crucial that the flap is centered over the
strength.13 Comparative results can also be found in a study by optical zone. It is important to practice centration of the suction
Alio et al., which suggests that the biomechanical effect of LASIK ring when using the femtosecond laser, using the pupil as the fixation
with the femtosecond laser is equivalent to the effects of surface point. It is also important that the suction ring is centered on the
ablation.14 computer screen of the laser prior to flap creation.

Stronger flaps are also a biomechanical advantage, and published Flap diameter should be based on the type of excimer laser used.
literature suggests that using flaps created using the femtosecond With the Alcon LADARVision CustomCornea Excimer Laser
laser are stronger than those created with a mechanical (Alcon, Ft Worth, Texas, USA), the maximum ablation zone is 6
microkeratome. Kim et al. studied the amount of force required mm, and the typical flap diameter ranges from 7-7.5 mm. With
to re-lift flaps created by a femtosecond laser and a mechanical the Bausch & Lomb Zyoptix Excimer Laser (Bausch & Lomb,
microkeratome, and concluded that a significantly greater amount Rochester, New York, USA), the typical flap diameter is 7.5 -8 mm.
of strength was needed to re-lift the femtosecond-laser flaps at 3 Although careful handling is required, which is the case with any
months post-operatively (P<0.05).3 An hypothesis by Marshall corneal flap, smaller corneal flaps tend to be easier to handle than
suggests that it is the manner in which the femtosecond laser flaps of 9 -10 mm, as they are less likely to tear or buttonhole.
creates the flap that results in a stronger flap, whereby micro-
photodisruption creates a surface that enables better adhesion SBK vs. PRK Clinical Study
between the corneal flap and the stromal bed.15 When using the
metal blade of a mechanical microkeratome, a smooth corneal We initiated a clinical study to evaluate SBK and compare it to
flap and stromal bed is created. Subsequently, the two surfaces PRK. In this contralateral study, 100 eyes of 50 patients were treated;
may slip against each other once the flap has been replaced, which one eye of each patient underwent femtosecond-laser assisted
can delay wound healing. LASIK (with an intended flap thickness of 100 µm), and the fellow
eye underwent PRK. The study took place at two centers, with 25
SBK: The best of LASIK and PRK patients treated at Kansas City and 25 patients treated at Houston.
Informed consent was obtained from all patients.
While the LASIK procedure and PRK both have significant
advantages, they are hindered by significant disadvantages. We The mean age of the patients was 33.24 ± 6.97 (range of 22 to 48)
created a procedure that combined the visual results and painless with 42% (n = 21) males and 58% (n = 29) females enrolled. Criteria
experience of the LASIK with the biomechanical stability of surface for inclusion included spherical myopia of -2 to -6.00 D, with up to
ablation, and called it sub-Bowman’s keratomileusis. Many -3.50 D refractive astigmatism; stable refraction for 1 year; a BSCVA
surgeons already perform laser vision correction with a of at least 20/20 in each eye; and an average central corneal thickness
femtosecond laser or a mechanical microkeratome, with flaps of e” 500 µm in each eye. As it was a contralateral study, the two
d”100 µm, but the SBK procedure boasts customized corneal flap groups were almost equal in terms of pre-operative mean refractive
creation. The key to this technique is to create a corneal flap that is error: the femtosecond laser group was -3.64 D (-2.00 to -5.75 D)
planar. Some mechanical microkeratomes can create a 100-µm (SD = 0.97) with a mean manifest cylindrical refraction of -0.63 D
flap, but the shape is more typically meniscus, which is why we (0 to -3.00 D), while the PRK group was -3.68 D (-2.00 to -5.75 D)
have a preference for corneal flap creation using the femtosecond (SD = 1.06) with a mean manifest cylindrical refraction of -0.64 D
laser.16 (0 to -2.75 D). Both groups had a mean pre-operative BSCVA of
20/17 with a range of 20/12 to 20/20 (SD = 2.47). Pre-operative
With the SBK procedure the diameter of the flap is based on the UCVA ranged from 20/80 to count fingers in both groups.
requirements of the individual patient and the type of excimer
laser used, with an intended thickness of between 90 and 110 µm. All patients underwent correction for myopia, with or without
In the clinical study we conducted to evaluate SBK vs. PRK, it was astigmatism, using the Alcon LADARVision 4000 Excimer Laser
necessary to standardize the flap thickness and diameter to an (Alcon Laboratories, Ft. Worth, TX) with a customized wavefront
intended flap thickness of 100 µm and a diameter of 8.5 mm. The treatment. For the SBK eyes, we used a small flap diameter (8.5
approach allows the preservation of as much Bowman’s membrane mm) and a thin flap (d”100 µm). All flaps in this procedure were
as possible, as well as avoiding disruption of the lamellae in the created using the 60-kHz femtosecond laser (IntraLase FS
periphery of the cornea. In our experience, with these thinner, Femtosecond Laser, Advanced Medical Optics, Irvine, CA), using
a raster pattern with the hinge located in the superior position.

34 DOS Times - Vol. 13, No.4, October 2007

The hinge angle was set at 50º and the side-cut angle was 75º. The corneal response factor (CRF) and ocular pulse amplitude. The
incidence of dense bubbles in the interface was decreased by evaluation showed that PRK had no biomechanical advantage over
enabling the e- “pocket” software. OCT measurements revealed a flap-based approach; corneal hysteresis decreased after both
that the femtosecond-laser flaps had a planar thickness with a SBK and PRK, and the CRF results indicated biomechanical
mean of 112 ± 5 µm (range 87 to 118 µm), with the average standard weakening seen in both the SBK and PRK eyes. This initial study
deviation in flap thickness at 4 µm. indicates that the SBK procedure offers refractive surgeons and
patients the best of both LASIK and PRK, while avoiding the
All patients received customized ablation. The PRK procedure disadvantages.
was performed with an 8.5-mm trephine placed on the eye, the
application of 20% ethanol for 25 seconds, followed by irrigation SBK in the Future
and chilling with balanced salt solution within the trephine. All
eyes received proparacaine 0.5% and tetracaine 0.5% drops intra- Although further clinical studies on the SBK procedure are
operatively. The goal of all surgeries was emmetropia. required, this hybrid technique, which combines LASIK and PRK,
cancels out the negatives of both procedures, leaving a single
Following surgery, all patients received a topical antibiotic drop, a superior method for performing corneal refractive surgery.
steroid drop and preservative-free tears. In the PRK eyes, a Combining the use of customized flaps with the SBK procedure,
bandage contact lens was placed and left on until the cornea re- using the femtosecond laser, achieves both efficacy and safety,
epithelialized. Topical antibiotic and steroids were applied four with the best possible visual results. The results of our study purport
times a day for post-operative week 1, as well as preservative-free that the SBK procedure is superior to PRK in almost every pertinent
artificial tears. The steroid was tapered to TID in the second week aspect, particularly in the immediate post-operative period, when
in the PRK eyes, followed by BID in the third week, and once a day considering visual results and patient feedback. Currently we can
thereafter. The PRK eyes also received Acular LS (ketorolac, customize the corneal flap thickness and diameter to cater to
Allergan, Irvine, CA) which did not exceed 3 times per day for the individual patients. In the future, surgeons will be able to create
first 3 days, in addition to acetaminophen/hydrocodone 1-2 tablets, ‘smart’ flaps, with the ability change the shape of the flap, taking
4-6 times per day for pain control. No topical anesthetic drops astigmatism into account, and adjust the flap edge based on the
were applied. thickness of the epithelium. The SBK procedure may constitute
the establishment of a new “K” in refractive surgery, and as studies
Although the full results of this study are due to be published later continue, the procedure may become an essential tool in the
this year, visual results for the SBK eyes have shown a quick return evolution of laser refractive surgery.
to functional vision with 100% of the 50 eyes achieving 20/40
uncorrected visual acuity on the first post-operative day, compared References
to 42% in the PRK eyes. At one month post-operatively, 88% of the
femtosecond eyes achieved 20/20 or better visual acuity, compared 1. Comprehensive Report on the Global Refractive Surgery Market.
to 48% of the PRK eyes. Also significant was the fact that the MarketScope 2006; Ballwin, MO.
femtosecond laser assisted eyes had lower levels of HOAs at 1 and
3 months post-operatively (coma and spherical aberration) than 2. Kurtz RM, Liu X, Elner VM, et al. Photodisruption in the human
the PRK eyes. cornea as a function of laser pulse width. J Refract Surg 1997; 13:653–
658.

It took up to 6 months for the PRK eyes to achieve the same level 3. Kim JY, Kim MJ, Kim TI, et al. A femtosecond laser creates a stronger
flap than a mechanical microkeratome. Invest Ophthalmol Vis Sci
of vision as the SBK eyes at 1 month post-operatively. Although
2006; 47:599–604.
the follow-up results of the two groups were relatively equal by six

months post-operatively, it is important to consider that patients 4. Montes-Mico R, Rodriguez-Galietero A, Alio JL. Femtosecond laser

make up their minds about how successful or unsuccessful their versus mechanical keratome LASIK for myopia. Ophthalmology

laser vision procedure was in the first few months, and they will 2007; 114:62–68.

talk to family and friends about their experience in the immediate 5. Binder PS. One thousand consecutive IntraLase laser in situ
post-operative period. keratomileusis flaps. J Cataract Refract Surg 2006; 32:962–969.

Patients expressed their preference for their femtosecond laser- 6. Kezirian GM, Stonecipher KG. Comparison of the IntraLase
treated eye to their PRK-treated eye, as the femtosecond eye caused
femtosecond laser and mechanical microkeratomes for laser in situ

less pain and achieved better visual results during the first 3 post- keratomileusis. J Cataract Refract Surg 2004; 30:804–811.

operative months. In fact, patients preferred the vision in their 7. Durrie DS, Kezirian GM. Femotsecond laser vesus
mechanicalmicrokeratome flaps in wavefront-guided laser in situ
SBK eye over their PRK eye out to three months by a margin of 2 keratomileusis: prospective contralateral eye study. J Cataract Refract
to 1. There was less sensitivity and fluctuation of vision through

one month in the SBK group, and the group also had better high Surg 2005; 31:120–126.

and low contrast acuity and retinal image quality, compared to the
PRK group. The SBK group achieved less dry eye, double vision 8. Tran DB, Sarayba MA, Bor Z, et al. Randomized prospective clinical
study comparing induced aberrations with IntraLase and Hansatome
and blurry vision, glares/halos, grittiness and difficulty with night flap creation in fellow eyes: potential impact on wavefront-guided
driving through three months post-operatively. laser in situ keratomileusis. J Cataract Refract Surg 2005; 31:97–

The Optical Response Analyzer (Reichert) and the Pascal Dynamic 105.

Contour Tonometer (SMT/Ziemer Ophthalmic Group) were used 9. J. Marshall et al., The effects of varying forms of corneal flap creation
to evaluate biomechanical results, by assessing corneal hysteresis,
on wound healing and biomechanics, unpublished data; J. Marshall

www.dosonline.org 35

et al., The impact of flap depth on corneal biomechanics and wound 13. Dupps WJ Jr, Wilson SE. Biomechanics and wound healing in the

healing in laser refractive surgery, unpublished data cornea. Exp Eye Res. 2006;83:709-20

10. Dupps WJ Jr, Wilson SE. Biomechanics and wound healing in the 14. J.L. Alio, Aberrometric outcomes and very high-frequency digital
cornea. Exp Eye Res. 2006;83:709-20. ultrasound evaluation of the flap thickness profile in LASIK surgery
using three different methods for lamellar keratotomy, unpublished
11. Deenadayalu C, Mobasher B, Rajan SD, et al. Refractive change data
induced by the LASIK flap in a biomechanical finite element model.
J Refract Surg 2006;22:286–292. 15. Marshall J. Femtosecond vs. epi-LASIK. Cataract & Refractive
Surgery Today Europe 2006; 1:44–49.
12. Alastrue V, Calvo B, Pena E, et al. Biomechanical modeling of
refractive corneal surgery. J Biomech Eng 2006; 128:150–160. 16. Flanagan GW, Binder PS. Precision of flap measurements for laser
in situ keratomileusis in 4428 eyes. J Refract Surg 2003;19:113-23.

First Author
Stephen G. Slade MD

Monthly Clinical Meetings Calendar 2007-2008

Centre for Sight Sir Ganga Ram Hospital
29th July, 2007 (Sunday) 25th November, 2007 (Sunday)

Dr. R.P. Centre for Ophthalmic Sciences Mohan Eye Institute
26th August, 2007 (Sunday) 30th December, 2007 (Sunday)

Dr. Shroff Charity Eye Hospital Venu Eye Institute
30th September, 2007 (Sunday) 20th January, 2008 (Sunday)

Guru Nanak Eye Centre Army Hospital (R&R)
28th October, 2007 (Sunday) 24th February, 2008 (Sunday)

Midterm Conference of DOS Safdarjung Hospital
17th,18th November, 2007 (Saturday - Sunday) March, 2008

36 DOS Times - Vol. 13, No.4, October 2007

Central Serous Retinopathy Retina

Bhuvan Chanana MD, Raj Vardhan Azad MD, FRCSEd

Central serous retinopathy (CSR) or Central serous 1 month of presentation as compared with 18% of control subjects.4
chorioretinopathy is an idiopathic, self limiting, non- Haimovici et al evaluated systemic risk factors for CSR in 312
inflammatory, serous detachment of the sensory retina resulting patients and 312 control subjects. Systemic steroid use and
from altered barrier and deficient pumping functions at the level pregnancy were most strongly associated with CSR. Other risk
of the retinal pigment epithelium (RPE). In some cases serous factors included antibiotic use, alcohol use, untreated hypertension,
detachments of the RPE may also be present. and allergic respiratory disorders.5

CSR is most common in male patients aged 20-55 years. This Cotticelli et al showed an association between Helicobacter pylori
condition affects men 6-10 times more often than it affects women. infection and CSR.6 The prevalence of H pylori infection was 78%
CSR is common among Caucasians, Hispanics, and Asians, and in patients with CSR compared with a prevalence of 43.5% in the
rare in African Americans. Patients may present with a later age of control group. The authors proposed that H pylori infection may
onset (>50 y). Spaide et al reviewed 130 consecutive patients with represent a risk factor in CSR, though no further studies have
CSCR and found the age range at first diagnosis to be 22.2-82.9 substantiated this claim.
years, with a mean age of 49.8 years.1 Patients diagnosed at 50
years or older are found to have bilateral disease, demonstrate a Natural course
decreased male predominance (2.6:1), and show more diffuse RPE
changes. Furthermore, these patients are more likely to have Most patients with CSR (80-90%) resolve spontaneously within 3
systemic hypertension or a history of corticosteroid use. to 4 months, with vision returning to 20/25 or better. Even with
return of good central visual acuity, many of these patients still
Pathophysiology notice dyschromatopsia, loss of contrast sensitivity,
metamorphopsia, or, rarely, nyctalopia.
Previous hypotheses for the pathophysiology have included
abnormal ion transport across the RPE and focal choroidal • Patients with classic CSR (characterized by focal leaks) have a
vasculopathy. ICG angiography has demonstrated both multifocal 40-50% risk of recurrence in the same eye.
choroidal hyperpermeability and hypofluorescent areas suggestive
of focal choroidal vascular compromise. Some investigators believe • Risk of choroidal neovascularization from previous CSR is
that initial choroidal vascular compromise subsequently leads to considered small (<5%) but has an increasing frequency in
secondary dysfunction of the overlying RPE. older patients diagnosed with CSR.

Studies employing multifocal electroretinography have • A subset of patients (5-10%) may fail to recover 20/30 or better
demonstrated bilateral diffuse retinal dysfunction even when CSR visual acuity. These patients often have recurrent or chronic
was active only in one eye. These studies support the belief of serous retinal detachments, resulting in progressive RPE
diffuse systemic effect on the choroidal vasculature. atrophy and permanent visual loss to 20/200 or worse. The
final clinical picture represents diffuse retinal pigment
Type A personalities, systemic hypertension, stress and obstructive epitheliopathy.
sleep apnea may be associated with CSR. The pathogenesis here is
thought to be elevated circulating cortisol and epinephrine, which
affects the autoregulation of the choroidal circulation.2
Furthermore, Tewari et al demonstrated that patients with CSCR
showed impaired autonomic response with significantly decreased
parasympathetic activity and significantly increased sympathetic
activity.3

Systemic associations of CSR include organ transplantation, Figure 1. Fundus photograph showing localized
exogenous steroid use, endogenous hypercortisolism (Cushing neurosensory detachment in the macula from
syndrome)2, systemic hypertension, systemic lupus erythematosus, central serous chorioretinopathy
pregnancy, gastroesophageal reflux disease, use of sildenafil citrate,
and use of psychopharmacologic medications. Corticosteroids have
a direct influence on the expression of adrenergic receptor genes
and, thus, contribute to the overall effect of catecholamines on the
pathogenesis of CSR. Consequently, multiple studies have
conclusively implicated the effect of corticosteroids in the
development of CSR. Carvalho-Recchia et al showed in a series
that 52% of patients with CSR had used exogenous steroids within

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

www.dosonline.org 39

Figure 2. Fluorescein angiography in the above patient.
A focal hyperfluorescent leak is present superior to fovea with gradual

leakage of fluorescein dye within the neurosensory detachment.

Clinical features Late sequelae of this fibrinous exudate include subretinal fibrosis,
CNV or RPE rips.
Patients typically present with acute symptoms of blurred and
dim vision, micropsia, or paracentral scotoma. In general, the vision Another atypical CSR includes inferior, peripheral, atrophic RPE
ranges from 20/20 to 20/200, but in most patients vision is better tracts (linear pigment lines) and is associated with a poorer
than 20/30. The decreased vision usually is improved by a small prognosis. Excessive or prolonged subretinal leakage is responsible
hyperopic correction. Other clinical signs include a delayed retinal for this type of CSR. Gravity causes the subretinal fluid to collect
recovery time following photostress, loss of color saturation, and inferiorly, forming a “teardrop” or “hourglass” shape. This severe
loss of contrast sensitivity. type of CSR is more common in persons of Hispanic or Asian
ancestry.
Slit lamp non-contact biomicroscopy or contact lens biomicroscopy
typically shows a round, well-delineated, shallow, serous macular Fluorescein Angiography of CSR
neurosensory detachment, which is often surrounded by a halo
light reflex, involving the posterior pole mainly macula (Figure 1). Three characteristic Fluorescein Angiographic patterns are seen
Subretinal fibrin precipitates may be seen as multiple, gray-white, in CSR:
dot like condensations on the posterior surface of the detached
retina. Small, round, yellow or gray serous RPE detachments • Expansile dot pattern
(PEDs) may be present. These serous PEDs are typically less than
a quarter of a disc diameter in size, are located in the superior half • Smokestack pattern
of the neurosensory detachment. RPE atrophy may be present in
one or both eyes as evidence of an active or previous CSR episode. • Diffuse pattern

An atypical variant of CSR usually is found in healthy middle-aged An expansile dot of hyperfluorescence is the most common
men and presents with multiple PEDs and multiple bullous serous presentation. A small, focal hyperfluorescent leak from the choroid
neurosensory detachments that demonstrate shifting fluid. These through the RPE appears in the early phase of the angiogram and
detachments are located in the midperiphery or more posteriorly. increases in size and intensity as the angiogram progresses
This form of CSR is characterized by a more fibrinous subretinal (Figure 2). In some patients, several leaking expansile dots may be
exudate that imparts an opaque appearance to the subretinal fluid. present. Smokestack pattern is uncommon, occurring in
approximately 10% of cases. The fluorescein starts with a central

40 DOS Times - Vol. 13, No.4, October 2007

spot of hyperfluorescence that spreads vertically and, finally, diffuse CSR from occult choroidal neovascularization (CNV)
laterally, in a configuration evocative of a plume of smoke. This in older individuals and idiopathic polypoidal choroidal
unique pattern is felt to be secondary to convection currents and a vasculopathy. Multiple patches of hyperfluorescence
pressure gradient between the protein concentration of the presumably are due to choroidal hyperpermeability, which,
subretinal fluid and the fluorescein dye entering the detachment. in later phases, results in silhouetting or negative staining of
larger choroidal vessels.
Rarely a diffuse pattern of fluorescein leakage is present, often
without any obvious leakage point. Patients with this condition Other Tests
have large, gravity dependent, serous detachment of the retina
and extensive RPE changes. • Multifocal electroretinography has been used to identify focal
regions of decreased retinal function, even in asymptomatic
Other Imaging Studies or clinically inactive eyes.7 Furthermore, investigators,
including Lai et al, are using multifocal electroretinography as
• Optical coherence tomography (OCT) reveals many aspects a means of assessing the efficacy and safety of new treatment
of the pathophysiology of CSR, ranging from subretinal fluid modalities for CSR.8
(Figure 3), pigment epithelial detachments, and retinal atrophy
following chronic disease. OCT is especially helpful in • Microperimetry (using the Nidek MP-1 microperimeter) has
identifying subtle, even subclinical, neurosensory macular also shown that, despite clinical resolution of CSR, there is
detachments (Figure 3). lower retinal sensitivity in the macula even once visual acuity
returned to 20/20. Fixation studies showed stability of central
• ICG angiography has shown hypofluorescent areas early in fixation.
the angiogram followed by late hyperfluorescence and leakage
in choroidal vasculature. Often, multiple areas of leakage are Medical Care
seen on ICG angiography that are not evident clinically or on
FA. ICG angiography can be useful to differentiate atypical • Psychopharmacologic agents (eg, anxiolytics, antidepressants)
were a risk factor for CSR. Corticosteroids may result in
exacerbation of serous detachments in CSR.

Figure 3. OCT showing fluid in the subretinal space from
central serous chorioretinopathy.

www.dosonline.org 41

• Acetazolamide has been suggested to hasten the resolution Patient Education
of subretinal fluid.
• If possible, patients should avoid stressful situations. Patient
• Tatham and Macfarlane described a case series of patients participation in stress-reducing activities (eg, exercise,
who were treated with propranolol for CSR.9 They suggested meditation, yoga) is recommended.
that beta-blockade had a hypothetical mechanism in treating
CSR. Further evidence is needed to substantiate this potential • Control of systemic hypertension may reduce the incidence
treatment. of CSR.

• Nielsen et al proposed the use of mifepristone in the treatment Complications
of chronic CSR in a case report.10
• A small minority of patients develops choroidal
• Intravitreal bevacizumab (Avastin) has been used to treat neovascularization at the site of leakage and laser treatments.11,
choroidal neovascularization following CSR. 12 A retrospective review of cases shows that one half of these
patients may have had signs of occult choroidal
Surgical Care neovascularization at the time of treatment. In the other
patients, the risk of choroidal neovascularization may have
Current treatment guidelines suggest that patients may be observed been increased by the laser treatment.
for at least 3-4 months in most first episodes of unilateral CSR.
Laser treatment induces rapid remission of subretinal fluid and • Acute bullous retinal detachment may occur in otherwise
shortens the course of the disease, but it does not appear to healthy patients with CSR. This appearance may mimic Vogt-
improve the final visual prognosis. Koyanagi-Harada disease or rhegmatogenous retinal
detachment.
Laser photocoagulation should be considered under the following
circumstances: • Recurrent attacks leads to RPE atrophy and subsequent retinal
atrophy.
• Persistence of a serous retinal detachment for more than 3-4
months Prognosis

• Recurrence in an eye with visual deficit from previous CSR • Typical serous retinal detachments resolve spontaneously in
most patients, with most patients (80-90%) returning to 20/25
• Presence of visual deficits in opposite eye from previous or better vision.
episodes of CSR
• Even with return of good central visual acuity, many of these
• Bilateral CSR for early rehabilitation patients still notice dyschromatopsia, loss of contrast
sensitivity, metamorphopsia, or nyctalopia.
• Occupational or other patient need requiring prompt recovery
of vision. • Patients with classic CSR (characterized by focal leaks) have a
40-50% risk of recurrence in the same eye.
• Patients with recurrent episodes of serous detachment with a
leak located more than 300 µm from the center of the fovea. • A subset of patients (5-10%) may fail to recover 20/30 or better
visual acuity. These patients often have atypical CSR, recurrent
Photodynamic therapy or chronic serous retinal detachments, resulting in progressive
RPE atrophy and permanent visual loss to 20/200 or worse.
Photodynamic therapy (PDT) has growing support in the literature The final clinical picture represents diffuse retinal pigment
as a treatment of chronic CSCR and, most recently, acute phases epitheliopathy.
of this condition. PDT is known to have a direct effect on the
choroidal circulation but was limited by potential adverse effects, • Risk of choroidal neovascularization from previous CSR is
such as macular ischemia. Authors, such as Lai et al, are describing considered small (<5%) but has an increasing frequency in
reduced dosing of verteporfin. The rates of adverse events have older patients diagnosed with CSR.
decreased significantly with these modifications. PDT is believed
to hasten both fluid resorption and visual recovery. Lai et al References
described the use of half dose verteporfin in the treatment of
CSR.8 They proposed 3 mg/m2 of verteporfin infused over 8 1. Spaide RF, Campeas L, Haas A, Yannuzzi LA, Fisher YL, Guyer DR,
minutes, followed 2 minutes later with ICG guided PDT. Of the et al. Central serous chorioretinopathy in younger and older
eyes treated, 85% showed complete resolution of the neurosensory adults. Ophthalmology. Dec 1996;103(12):2070-9.
retinal detachment and/or pigment epithelial detachment by 1
month after treatment. 2. Bouzas EA, Scott MH, Mastorakos G, Chrousos GP, Kaiser-Kupfer
MI. Central serous chorioretinopathy in endogenous
Further Outpatient Care hypercortisolism. Arch Ophthalmol. Sep 1993;111(9):1229-33.

• Most patients receive follow-up care for 2 months to 3. Tewari HK, Gadia R, Kumar D, Venkatesh P, Garg SP. Sympathetic-
determine whether the fluid resolves spontaneously. parasympathetic activity and reactivity in central serous
chorioretinopathy: a case-control study. Invest Ophthalmol Vis
• If laser is performed, follow-up within 3-4 weeks should be Sci. Aug 2006; 47(8): 3474-8.
done to determine the rare complication of post laser CNV.11
4. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, Spaide RF, Freund
KB, Rodriguez-Coleman H, et al. Corticosteroids and central serous

42 DOS Times - Vol. 13, No.4, October 2007

chorioretinopathy. Ophthalmology. Oct; 2002; 109(10):1834-7. 9. Tatham A, Macfarlane A. The use of propranolol to treat central

5. Haimovici R, Koh S, Gagnon DR, Lehrfeld T, Wellik S. Risk factors serous chorioretinopathy: an evaluation by serial OCT. J Ocul
for central serous chorioretinopathy: a case-control Pharmacol Ther. Apr 2006; 22(2):145-9.

study. Ophthalmology. Feb 2004; 111(2):244-9. 10. Nielsen JS, Weinreb RN, Yannuzzi L, Jampol LM. Mifepristone

6. Cotticelli L, Borrelli M, D’Alessio AC, Menzione M, Villani A, Piccolo treatment of chronic central serous chorioretinopathy.
G, et al. Central serous chorioretinopathy and Helicobacter pylori. Eur Retina. Jan 2007; 27(1):119-22.

J Ophthalmol. Mar-Apr 2006; 16(2):274-8. 11. Gomolin JE. Choroidal neovascularization and central serous

7. Marmor MF, Tan F. Central serous chorioretinopathy: bilateral chorioretinopathy. Can J Ophthalmol. Feb 1989; 24(1):20-3.

multifocal electroretinographic abnormalities. Arch 12. Matsunaga H, Nangoh K, Uyama M, Nanbu H, Fujiseki Y, Takahashi
Ophthalmol. Feb 1999; 117(2):184-8. K. [Occurrence of choroidal neovascularization following

8. Lai TY, Chan WM, Li H, Lai RY, Liu DT, Lam DS. Safety enhanced photocoagulation treatment for central serous retinopathy]. Nippon
photodynamic therapy with half dose verteporfin for chronic central Ganka Gakkai Zasshi. Apr 1995; 99(4):460-8.

serous chorioretinopathy: a short term pilot study. Br J

Ophthalmol. Jul 2006; 90(7):869-74.

Author
Raj Vardhan Azad MD, FRCSEd

www.dosonline.org 43

Current Concepts in Retinoblastoma Ocular Tumours

Santosh G. Honavar MD, FACS

Retinoblastoma is the most common intraocular malignancy Genetic counseling is an important aspect in the management of
in children, with a reported incidence ranging from 1 in 15,000 retinoblastoma. In patients with a positive family history, 40% of
to 1 in 18,000 live births.1 It is bilateral in about 25 to 35% of cases.2 the siblings would be at risk of developing retinoblastoma and
The average age at diagnosis is 18 months, with unilateral cases 40% of the offspring of the affected patient may develop
being diagnosed at around 24 months and bilateral cases before retinoblastoma. In patients with no family history of
12 months.2 retinoblastoma, if the affected child has unilateral retinoblastoma,
1% of the siblings are at risk and 8% of the offspring may develop
Early tumor recognition aided by indirect ophthalmoscopy and retinoblastoma. In cases of bilateral retinoblastoma with no positive
refined enucleation technique contributed to an improved survival family history, 6% of the siblings and 40% of the offspring have a
from 5% in 1896 to 81% in 1967.1-4 Advances in external beam chance of developing retinoblastoma. 2
radiotherapy in the 1970s and further progress in planning and
delivery in the next two decades provided an excellent alternative Clinical Manifestations of Retinoblastoma
to enucleation and resulted in substantial eye salvage.2 Focal
measures such as cryotherapy, photocoagulation and plaque Leucocoria is the most common presenting feature of
brachytherapy allowed targeted treatment of smaller tumors retinoblastoma, followed by strabismus, painful blind eye and loss
optimizing vision salvage.2 Parallel advancements in ophthalmic of vision. Table 1 lists the common presenting signs and symptoms
diagnostics such as ultrasonography, computed tomography, and of retinoblastoma. 21
magnetic resonance imaging contributed to improved diagnostic
accuracy and early detection of extraocular retinoblastoma. The clinical presentation of retinoblastoma depends on the stage
of the disease.10 Early lesions are likely to be missed, unless an
The recent advances such as identification of genetic mutations5, 6 indirect ophthalmoscopy is performed. The tumor appears as a
replacement of external beam radiotherapy by chemoreduction translucent or white fluffy retinal mass (Figure 1). The child may
as the primary management modality, use of chemoreduction to present with strabismus if the tumor involves the macula or with
minimize the size of regression scar with consequent optimization reduced visual acuity.
of visual potential, 7-11 identification of histopathologic high-risk
factors following enucleation 12 and provision of adjuvant therapy
to reduce the incidence of systemic metastasis, 13 protocol-based
management of retinoblastoma with accidental perforation or
intraocular surgery 14-16 and aggressive multimodal therapy in the
management of orbital retinoblastoma 17,18 have contributed to
better survival, improved eye salvage and potential for optimal
visual recovery.

Genetics of Retinoblastoma

Out of the newly diagnosed cases of retinoblastoma only 6% are
familial while 94% are sporadic.2,19 Bilateral retinoblastomas involve
germinal mutations in all cases. Approximately 15% of unilateral
sporadic retinoblastoma is caused by germinal mutations affecting
only one eye while the 85% are sporadic.2

In 1971, Knudson proposed the two hit hypothesis.20 He stated Figure 1. Early manifestation of retinoblastoma
that for retinoblastoma to develop, two chromosomal mutations with a localized tumor at the posterior pole
are needed. In hereditary retinoblastoma, the initial hit is a germinal
mutation, which is inherited and is found in all the cells. The second Moderately advanced lesions usually present with leucocoria due
hit develops in the somatic retinal cells leading to the development to the reflection of light by the white mass in the fundus (Figure 2).
of retinoblastoma. Therefore, hereditary cases are predisposed to As the tumor grows further, three patterns are usually seen: 10
the development of nonocular tumors such as osteosarcoma. In
unilateral sporadic retinoblastoma, both the hits occur during the
development of the retina and are somatic mutations. Therefore
there is no risk of second nonocular tumors.

Ocular Oncology Service, • Endophytic, in which the tumor grows into the vitreous cavity
LV Prasad Eye Institute, LV Prasad Marg, (Figure 3). A yellow white mass progressively fills the entire
vitreous cavity and vitreous seeds occur. The retinal vessels
Banjara Hills, Hyderabad are not seen on the tumor surface.

www.dosonline.org 45

Figure 2. Lecocoria is the most common clinical Figure 3. Endophytic tumor with vitreous seeds
presentation of retinoblastoma

Figure 5. Diffuse infiltrative retinoblastoma with
placoid retinal thickening seen on gross examination

of the enucleated eye in a 7-year-old child.

Figure 4. Exophytic retinal tumor with
exudative retinal detachment

Table 1. Common presenting features of retinoblastoma

1. Leucocoria 56%

2. Strabismus 20%

3. Red painful eye 7%

4. Poor vision 5%

5. Asymptomatic 3%

6. Orbital Cellulitis 3%

7. Unilateral Mydriasis 2%

Figure 6. Retinoblastoma with orbital 8. Heterochromia Iridis 1%
extension in a 3-year-old child. 9. Hyphema 1%

• Exophytic, in which the tumor grows towards the subretinal a mass. This is generally seen in older children and usually

space (Figure 4). Retinal detachment usually occurs and retinal there is a delay in the diagnosis (Figure 5).

vessels are seen over the tumor. Advanced tumors manifest with proptosis secondary to optic nerve

• Diffuse infiltrating tumor, in which the tumor diffusely involves extension or orbital extension (Figure 6) and systemic metastasis.10

the retina causing just a placoid thickness of the retina and not Retinoblastoma can spread through the optic nerve with relative

46 DOS Times - Vol. 13, No.4, October 2007

Figure 7. A 5-year-old child with retinoblastoma Figure 8. A 4-year-old with spontaneous hyphema
with anterior segment seeding manifesting in the left eye. Ultrasonography confirmed the
with tumor hypopyon diagnosis of retinoblastoma.

Figure 9. Spontaneous vitreous Figure 10. An 18-month-old child with bilateral
hemorrhage as the presenting feature of retinoblastoma. The right eye has secondary glaucoma

retinoblastoma in a 4-year-old child and enlarged cornea while the left eye is phthisical.

ease especially once the lamina cribrosa is breached. Orbital
extension may present with proptosis and is most likely to occur at
the site of the scleral emissary veins. Systemic metastasis occurs to
the brain, skull, distant bones and the lymph nodes.

Some of the atypical manifestations of retinoblastoma include
pseudohypopyon (Figure 7), spontaneous hyphema (Figure 8),
vitreous hemorrhage (Figure 9), phthisis bulbi (Figure 10) and
preseptal or orbital cellulites (Figure 11). 10

Diagnosis of Retinoblastoma

A thorough clinical evaluation with careful attention to details, Figure 11. A 3-year-old child with retinoblastoma
aided by ultrasonography B-scan helps in the diagnosis. 10 presenting with orbital cellulites
Computed tomography and magnetic resonance imaging are
generally reserved for cases with atypical manifestations and
diagnostic dilemma and where extraocular or intracranial tumor
extension is suspected.10

A child with suspected retinoblastoma necessarily needs complete ophthalmoscope is diagnostic of retinoblastoma in over 90% of
ophthalmic evaluation including a dilated fundus examination cases.21 RetCam is a wide-angle fundus camera, useful in accurately
under anaesthesia.10 The intraocular pressure is measured and documenting retinoblastoma and monitoring response to therapy
the anterior segment is examined for neovascularization, (Figure 12).
pseudohypopyon, hyphema, and signs of inflammation.10Bilateral
fundus examination with 360 degree scleral depression is Ultrasonography B-scan shows a rounded or irregular intraocular
mandatory. Direct visualization of the tumor by an indirect mass with high internal reflectivity representing typical intralesional

www.dosonline.org 47

Figure 12. RetCam, a wide-angle digital Figure 13. Ultrasonography B-scan showing
fundus camera and image archival system multifocal retinal tumors
helps in documentation and assessment

of tumor regression on follow-up

calcification (Figure 13).10 Computed tomography delineates prognosis and cost-effectiveness of treatment in a given economic
extraocular extension and can detect an associated pinealoblastoma situation.
(Figure 14).10 Magnetic resonance imaging is specifically indicated
if optic nerve invasion or intracranial extension is suspected.10 On Intraocular Retinoblastoma
fluorescein angiography, smaller retinoblastoma shows minimally
dilated feeding vessels in the arterial phase, blotchy A majority of children with retinoblastoma manifest at the stage
hyperfluorescence in the venous phase and late staining (Figure when the tumor is confined to the eye. About 90-95% of children
15).10 in developed countries present with intraocular retinoblastoma
while 60-70% present at this stage in the developing world.10
Management of Retinoblastoma Diagnosis of retinoblastoma at this state and appropriate
management are crucial in life, eye and possible vision salvage.
The management of retinoblastoma needs a multidisciplinary team
approach including an ocular oncologist, pediatric oncologist, Classification of Intraocular Retinoblastoma
radiation oncologist, radiation physicist, and an ophthalmic
oncopathologist. The management strategy depends on the stage The Reese Ellsworth classification was introduced to prognosticate
of the disease – intraocular retinoblastoma, retinoblastoma with patients treated with methods other than enucleation.22 This
high-risk characteristics, orbital retinoblastoma and metastatic classification was devised prior to the widespread use of indirect
retinoblastoma. ophthalmoscopy and focal measures of management of
retinoblastoma. Although the Essen classification addressed some
Management of retinoblastoma is highly individualized and is based of the shortcomings of Reese Ellsworth classification, it is considered
on several considerations - age at presentation, laterality, tumor too complex. Further, none of the older systems of classification
location, tumor staging, visual prognosis, systemic condition, family had been designed to prognosticate chemoreduction, the current
and societal perception, and, to a certain extent, the overall favored method of retinoblastoma management. The new
International Classification of Intraocular Retinoblastoma is a

Figure 14. Computed tomography scan shows Figure 15. Fundus fluorescein angiography in
pinealoblastoma retinoblastoma in the early phase shows blotchy

48 hyperfluorescence

DOS Times - Vol. 13, No.4, October 2007

Table 2. International Classification of Intraocular Cryotherapy administered 2-3 hours prior to chemotherapy can
Retinoblastoma increase the delivery of chemotherapeutic agents across the blood
retinal barrier and thus has synergistic effect.10
Group A. Small tumors (< 3 mm) outside macula
Laser photocoagulation
Group B. Bigger tumors (> 3 mm) or any tumor in macula
or any tumor with subretinal fluid Laser photcoagulation is used for small posterior tumors 4 mm in
basal diameter and 2 mm in thickness.2,10The treatment is directed
Group C. Localized seeds (subretinal or vitreous) to delimit the tumor and coagulate the blood supply to the tumor
by surrounding it with two rows of overlapping laser burns.
Group D. Diffuse seeds (subretinal or vitreous) Complications include transient serous retinal detachment, retinal
vascular occlusion, retinal hole, retinal traction, and preretinal
Group E. Tumor touching the lens, Neovascular glaucoma, fibrosis. It is less often employed now with the advent of
Tumor anterior to anterior vitreous face involving ciliary thermotherapy. In fact, laser photocoagulation is contraindicated
body or anterior segment, Diffuse infiltrating retinoblastoma, while the patient is on active chemoreduction protocol. 10
Opaque media from hemorrhage, Tumor necrosis with
aseptic orbital cellulitis, and Phthisis bulbi Thermotherapy

logical flow of sequential tumor grading that linearly correlates In thermotherapy, focused heat generated by infrared radiation is
with the outcome of newer therapeutic modalities (Table 2).23, 24 applied to tissues at subphotocoagulation levels to induce tumor
This classification is currently being validated.25 necrosis.26 The goal is to achieve a slow and sustained temperature
range of 40 to 60 degree C within the tumor, thus sparing damage
Management of Intraocular Retinoblastoma to the retinal vessels (Figure 17). Transpupillary thermotherapy
using infrared radiation from a semiconductor diode laser delivered
The primary goal of management of intraocular retinoblastoma is with a 1300-micron large spot indirect ophthalmoscope delivery
to save life. Salvage of the organ (eye) and function (vision) are the system has become a standard practice. It can also be applied
secondary and tertiary goals respectively. There are several transpupillary through an operating microscope or by the
methods to manage intraocular retinoblastoma - focal (cryotherapy, transscleral route with a diopexy probe. The tumor is heated until
laser photocoagulation, transpupillary thermotherapy, transcleral it turns a subtle gray. Thermotherapy provides satisfactory control
thermotherapy, plaque brachytherapy), local (external beam for small tumors - 4 mm in basal diameter and 2 mm in thickness.
radiotherapy, enucleation), and systemic (chemotherapy). While Complete tumor regression can be achieved in over 85% of tumors
primary focal measures are mainly reserved for small tumors, using 3-4 sessions of thermotherapy.26The common complications
local and systemic modalities are used to treat advanced are focal iris atrophy, focal paraxial lens opacity, retinal traction
retinoblastoma. and serous retinal detachment. The major application of
thermotherapy is as an adjunct to chemoreduction. The application
Cryotherapy of heat amplifies the cytotoxic effect of platinum analogues. This
synergistic combination with chemoreduction protocol is termed
Cryotherapy is performed for small equatorial and peripheral chemothermotherapy.
retinal tumors measuring up to 4 mm in basal diameter and 2 mm
in thickness.2, 10 Triple freeze thaw cryotherapy is applied at 4-6 Plaque Brachytherapy
week intervals until complete tumor regression. Cryotherapy
produces a scar much larger than the tumor (Figure 16). Plaque brachytherapy involves placement of a radioactive implant
Complications of cryotherapy include transient serous retinal on the sclera corresponding to the base of the tumor to
detachment, retinal tear and rhegmatogenous retinal detachment. transsclerally irradiate the tumor.27 Commonly used radioactive
materials include Ruthenium 106 (Figure 18) and Iodine 125. The

Figure 16. A peripheral retinal tumor that
underwent Cryotherapy (left). The tumor has
completely regressed but the scar is much larger than

the tumor itself (right)

www.dosonline.org 49

Figure 17. Three focal tumors treated with Figure 18. Ruthenium 106 plaque.
transpupillary thermotherapy: Note flat scars

with patent blood vessels coursing through
the scars. Transpupillary thermotherapy classically

spares the blood vessels from occlusion and
produces a compact scar.

Table 3. Special considerations for enucleation in
retinoblastoma

a. Minimal manipulation

b. Avoid perforation of the eye

c. Harvest long (> 15 mm) optic nerve stump

d. Inspect the enucleated eye for macroscopic extraocular
extension and optic nerve involvement

e. Harvest fresh tissue for genetic studies

f. Avoid biointegrated implant if postoperative radiotherapy Figure 19. Osteosarcoma of the frontal
is necessary bone in a 20-year-old patient with bilateral

advantages of plaque brachytherapy are focal delivery of radiation retinoblastoma who had undergone
with minimal damage to the surrounding normal structures, external beam radiotherapy at 1-year age.
minimal periorbital tissue damage, absence of cosmetic
abnormality because of retarded bone growth in the field of from 4000-5000 cGy. The plaque is sutured to the sclera after
irradiation as occurs with external beam radiotherapy, reduced confirming tumor centration and is left in situ for the duration of
risk of second malignant neoplasm and shorter duration of exposure, generally ranging from 36 to 72 hours. The results of
treatment. plaque brachytherapy are gratifying with about 90% tumor control.
The common complications are radiation papillopathy and
Plaque brachytherapy is indicated in tumors less than 16 mm in radiation retinopathy.
basal diameter and less than 8 mm thickness. It could be the primary
or secondary modality of management. Primary plaque External Beam Radiotherapy
brachytherapy is currently performed only in situations where
chemotherapy is contraindicated. It is most useful as secondary External beam radiotherapy was the preferred form of
treatment in eyes that fail to respond to chemoreduction and management of moderately advanced retinoblastoma in late
external beam radiotherapy or for tumor recurrences. 1900s.28, 29 However with the advent of newer chemotherapy
protocols, external beam radiotherapy is being used less often.
Plaque brachytherapy requires precise tumor localization and Presently it is indicated in eyes where primary chemotherapy and
measurement of its basal dimensions. The tumor thickness is local therapy has failed, or rarely when chemotherapy is
measured by ultrasonography. The data is used for dosimetry on contraindicated. 10
a three-dimensional computerized tumor modeling system. The
plaque design is chosen depending on the basal tumor dimensions, The major problems with external beam radiotherapy are the
its location, and configuration. The dose to the tumor apex ranges stunting of the orbital growth, dry eye, cataract, radiation

50 DOS Times - Vol. 13, No.4, October 2007

Figure 20. Enucleated eyeball showing 18 mm optic Figure 21. Enucleated eyeball
nerve stump. Note the proximal portion of the optic showing extrascleral
tumor extension.
nerve is thickened indicating tumor infiltration.

retinopathy and optic neuropathy. External beam radiotherapy Figure 22.Retinoblastoma in the right eye following
can induce second malignant neoplasm especially in patients with enucleation with orbital implant by the
the hereditary form of retinoblastoma (Figure 19). There is a high
30% chance of developing another malignancy by the age of 30 myoconjunctival technique (left). Excellent cosmesis
years in such patients if they are given external beam radiotherapy follwing fitting of a custom ocular prosthesis (right).
compared to a less than 6% chance in those who do not receive
external beam radiotherapy.30 The risk of second malignant Minimum-manipulation surgical technique should be necessarily
neoplasm is greater in children under 12 months of age.30 practiced.11 It is important not to accidentally perforate the eye.
The sclera is thin at the site of muscle insertions and the rectus
Enucleation muscles have to be hooked delicately. It is important to obtain a
long optic nerve stump, ideally more than 15 mm, but never less
Enucleation is a common method of managing advanced than 10 mm (Figure 20).11 Certain steps can be taken to obtain
retinoblastoma. Just about 3 decades ago, a majority of patients about 15 mm long optic nerve stump in all cases of advanced
with unilateral retinoblastoma and the worse eye in bilateral retinoblastoma.11 Gentle traction can be applied by the traction
retinoblastoma underwent primary enucleation. A substantial sutures applied to recti muscle stumps prior to transecting the
reduction in the frequency of enucleation has occurred in the late optic nerve. As an alternative to the traction sutures, medial or
last century.31 Concurrently, there has been an increase in the use lateral rectus muscle stumps may be kept long and traction exerted
of alternative eye- and vision-conserving methods of treatment.9,32 with an artery clamp. A 15-degree curved and blunt-tipped

Primary enucleation continues to be the treatment of choice for
advanced intraocular retinoblastoma with neovascularization of
iris, secondary glaucoma, anterior chamber tumor invasion, tumors
occupying >75% of the vitreous volume, necrotic tumors with
secondary orbital inflammation, and tumors associated with
hyphema or vitreous hemorrhage where the tumor characteristics
can not be visualized, especially when only one eye is involved.10

Figure 23. Macular retinoblastoma in a 6-month-old child (left), 51
completely regressed with 6 cycles of chemoreduction alone (right).

www.dosonline.org

Table 4. Chemoreduction regimen and doses for intraocular Placement of an orbital implant following enucleation for
retinoblastoma retinoblastoma is the current standard of care. The orbital implant
promotes orbital growth, provides better cosmesis and enhances
Day 1: Vincristine + Etoposide + Carboplatin prosthesis motility. The implants could be non-integrated
(polymethyl methacrylate or silicon) or bio-integrated
Day 2: Etoposide (hydroxyapatite or porous polyethylene). Placement of a
biointegrated implant is generally avoided if post-operative
Standard dose: (3 weekly, 6 cycles): Vincristine 1.5 mg/m2 adjuvant radiotherapy is considered necessary. 11 Although most
(0.05 mg/kg for children < 36 months of age and implants structurally tolerate radiotherapy well, implant
maximum dose < 2mg), Etoposide 150 mg/m2 (5 mg/ vascularization may be compromised by radiotherapy thus
kg for children < 36 months of age), Carboplatin 560 increasing the risk of implant exposure. Use of myoconjunctival
mg/m2 (18.6 mg/kg for children < 36 months of age) technique and custom ocular prosthesis have optimized prosthesis
motility and static cosmesis (Figure 22).
High-dose (3 weekly, 6-12 cycles): Vincristine 0.025 mg/Kg,
Etoposide 12 mg/Kg, Carboplatin 28 mg/Kg Chemotherapy

tenotomy scissors is introduced from the lateral aspect (or a straight Chemoreduction, defined as the process of reduction in the tumor
scissors from the medial aspect) and the optic nerve is palpated volume with chemotherapy, has become an integral part of the
with the closed tip of the scissors while maintaining gentle traction current management of retinoblastoma.32 Chemotherapy alone is
on the eyeball. The scissors is moved posteriorly to touch the however not curative and must be associated with intensive local
orbital apex while “strumming” the optic nerve. The scissors is therapy. Chemoreduction coupled with focal therapy can minimize
lifted by 3 or 4 millimeters off the orbital apex (to preserve the the need for enucleation or external beam radiotherapy without
contents of the superior orbital fissure), the blades of the scissors significant systemic toxicity.
are opened to engage the optic nerve, and the nerve is transected Chemoreduction in combination with focal therapy is now
with one bold cut. This maneuver generally provides at least 15 extensively used in the primary management of retinoblastoma.
mm long optic nerve stump.11 Enucleation spoon and heavy 33-36There are different protocols in chemotherapy. The commonly
enucleation scissors limit space for maneuverability and may result used drugs are vincristine, etoposide and carboplatin, for 6 cycles.
in a shorter optic nerve stump. In addition, one should be careful 7-10 (Table 4) Standard dose chemoreduction is provided in Reese
not to accidentally perforate the eye during enucleation. The Ellsworth groups I-IV. 10In high dose chemoreduction, the dose of
enucleated eyeball is inspected for optic nerve (Figure 20) or etoposide and carboplatin is increased. This is indicated in Reese
extraocular extension (Figure 21) of tumor. Ellsworth group V tumors. 10

Eyes manifesting tumor necrosis with aseptic orbital cellulitis pose With chemoreduction and sequential local therapy, it is now
specific problem. These patients should be imaged to rule out possible to salvage many an eye and maximize residual vision.
extraocular extension. Enucleation is best performed when the Chemoreduction is most successful for tumors without associated
inflammation is resolved. 11 A brief course of preoperative oral subretinal fluid or vitreous seeding.7,8 Risk factors for tumor,
and topical steroids help control inflammation. Patients with subretinal seed and vitreous seed recurrence, and failure of
retinoblastoma presenting as phthisis bulbi need imaging to chemoreduction leading to external beam radiotherapy and/or
exclude extraocular and optic nerve extension. 11Phthisis generally enucleation have been identified.7, 8 Chemoreduction offers
results following spontaneous tumor necrosis and an episode of satisfactory tumor control for Reese Ellsworth groups I-IV eyes,
aseptic intraocular and orbital inflammation. Enucleation in these with treatment failure necessitating additional external beam
cases is often complicated by excessive peribulbar fibrosis and radiotherapy in only 10% and enucleation in 15% at 5-year follow-
intraoperative bleeding. 11 up. Patients with Reese Ellsworth group V eyes require external
beam radiotherapy in 47% and enucleation in 53% at 5 years.7, 8

Figure 24. Multifocal retinoblastoma (left) following
chemoreduction and transpupillary thermotherapy (right). Note

flat scars that are much smaller than the original tumor.

52 DOS Times - Vol. 13, No.4, October 2007

Figure 25. A juxtapapillary retinal tumor in a 9-month-old child (left) partially regressed with 3 cycles of
chemoreduction (middle) and completely regressed with 6 cycles of chemoreduction and transpupillary

thermotherapy (right). Note the completely exposed fovea following treatment, thus maximizing visual potential.

Chemoreduction is an option for selected eyes with unilateral
retinoblastoma.9

Figure 23 shows a tumor involving the macula at presentation.
With chemoreduction and transpupillary thermotherapy, there
was complete tumor regression. Figure 24, 25 and 26 show that
the resulting scar with chemoreduction was much smaller than
the original tumor with the foveola fully exposed, thus maximizing
visual potential.

It is important to be aware of the adverse effects and interactions Figure 26. Multifocal retinoblastoma (top) regressed
of chemotherapeutic agents, which include myelosuppression, following chemoreduction and transpupillary
febrile episodes, neurotoxicity and non-specific gastrointestinal thermotherapy (bottom).
toxicity. Chemotherapy should be given only under the supervision
of an experienced pediatric oncologist. early results have shown that periocular chemotherapy achieves
70% eye salvage in patients with Reese Ellsworth group VB
Periocular chemotherapy retinoblastoma (Figure 27).37

Carboplatin delivered deep posterior subtenons has been
demonstrated to be efficacious in the management of Reese
Ellsworth Group VB retinoblastoma with vitreous seeds because
it can penetrate the sclera and achieve effective concentrations in
the vitreous cavity. This modality is currently under trial. Our

Table 5. Histopathologic high-risk factors predictive of Follow-up Schedule
metastasis
The usual protocol is to schedule the first examination 3–6 weeks
• Anterior chamber seeding after the initial therapy. In cases where chemoreduction therapy
• Iris infiltration has been administered, the examination should be done every 3
• Ciliary body infiltration weeks with each cycle of chemotherapy. Patients under focal therapy
• Massive choroidal infiltration are evaluated and treated every 4-8 weeks until complete tumor
• Invasion of the optic nerve lamina cribrosa regression. Following tumor regression, subsequent examination
• Retrolaminar optic nerve invasion should be 3 monthly for the first year, 6 monthly for three years or
• Invasion of optic nerve transection until the child attains 6 years of age, and yearly thereafter.
• Scleral infiltration
• Extrascleral extension High Risk Retinoblastoma

Systemic metastasis is the main cause for mortality in patients
with retinoblastoma. Although the life prognosis of patients with
retinoblastoma has dramatically improved in the last three decades,
with a reported survival of more than 90% in developed countries,38
mortality is still as high as 50% in the developing nations.39,40
Reduction in the rate of systemic metastasis by identification of
high-risk factors and appropriate adjuvant therapy may help
improve survival.

www.dosonline.org 53

Retinoblastoma with massive vitreous seeds

(Figure 27a, left). Following 3 cycles of (Figure 27a, right). The tumor is partially regressed but
high-dose chemoreduction. the vitreous seeds persist. With periocular carboplatin
injection in addition to high dose chemoreduction, the
vitreous seeds show complete regression.

Figure 28. Histopathology of retinoblastoma showing Figure 29. Histopathology of retinoblastoma
anterior chamber seeding, iris infiltration, trabecular showing massive choroidal infiltration, scleral

meshwork infiltration and ciliary body invasion. infiltration and extrascleral extension.

Figure 30. Histopathology of retinoblastoma Figure 31. Histopathology of retinoblastoma showing
showing infiltration of the optic nerve beyond optic nerve infiltration to the level of transection.

the lamina cribrosa. DOS Times - Vol. 13, No.4, October 2007

High–Risk Factors

None of the clinical high-risk factors seem to strongly correlate
with mortality. Recent studies have evaluated the role of
histopathologic high-risk factors identified following enucleation.
The identification of frequency and significance of high-risk
histopathologic factors (Figures 28-31) that can reliably predict
metastasis is vital for patient selection for adjuvant therapy. Several
studies have addressed this issue.39, 41-49 It is now generally agreed

54

Figure 32. Primary orbital retinoblastoma manifesting with proptosis (left). Computed tomography
scan shows massive orbital tumor (right).

Figure 33. Secondary orbital retinoblastoma following enucleation, manifesting with extrusion
of the prosthetic eye (left). CT can shows an orbital tumor (right).

that massive choroidal infiltration, retrolaminar optic nerve subset of patients with unilateral sporadic retinoblastoma who
invasion, invasion of the optic nerve to transection, scleral underwent primary enucleation. The study used specific
infiltration, and extrascleral extension are the risk factors that are predetermined histopathologic characteristics for patient selection.
predictive of metastasis (Table 5).39, 41-49 A minimum follow-up of 1 year was allowed to include metastatic
events that generally occur at a mean of 9 months following
The reported occurrence of anterior chamber seeding (7%),45 enucleation.13, 50 The incidence of metastasis was 4% in those who
massive choroidal infiltration (12-23%),43-49invasion of optic nerve received adjuvant therapy compared to 24% in those who did not.
lamina cribrosa (6-7%),43-49 retrolaminar optic nerve invasion (6- The study found that administration of adjuvant therapy
12%),43-49 invasion of optic nerve transection (1-25%),43-49 scleral significantly reduced the risk of metastasis in patients with high-
infiltration (1-8%),43-49and extrascleral extension (2-13%),43-49widely risk histopathologic characteristics.
vary even in developed countries. Vemuganti and associates have
reported that 21% of the 76 eyes enucleated for advanced Our current practice is to administer 6 cycles of a combination of
retinoblastoma in India had anterior chamber seeding, 54% had carboplatin, etoposide and vincristine (identical to the protocol
massive choroidal infiltration, 46% had optic nerve invasion at or used for chemoreduction of intraocular retinoblastoma)in patients
beyond the lamina cribrosa and 7% had scleral infiltration or with histopathologic high-risk characteristics. All patients with
extrascleral extension. 12 It is apparent that the incidence of extension of retinoblastoma up to the level of optic nerve
histopathologic risk factors is strikingly high in developing countries transection, scleral infiltration, and extrascleral extension receive
compared to the published data from developed countries. high dose chemotherapy for 12 cycles and fractionated 4500 to
5000 cGy orbital external beam radiotherapy.
Adjuvant Therapy
Orbital Retinoblastoma
Studies on the efficacy of adjuvant therapy to minimize the risk of
metastasis initiated in the 1970s were marked by variable results Orbital retinoblastoma is rare in developed countries. Ellsworth
and provided no firm recommendation.18 A recent study with a observed a steady decline in the incidence of orbital retinoblastoma
long-term follow-up provides useful information.13, 50 It included a in his large series of 1160 patients collected over 50 years.51Orbital

www.dosonline.org 55

Figure 34. A child with retinoblastoma misdiagnosed as traumatic hyphema in
the left eye and treated with hyphema drainage

without a baseline ultrasonograpy evaluation presents after 1 year with extraocular
extension (left) and regional lymph node metastasis (right).

retinoblastoma is relatively more common in the developing with or without nodular optic nerve sheath are clinical indicators
countries. In a recent large multi-center study from Mexico, 18% of optic nerve extension of retinoblastoma that should be
of 500 patients presented with an orbital retinoblastoma.52 A recognized during enucleation.
Taiwanese group reported that 36% (42 of 116) of their patients
manifested with orbital retinoblastoma.53 The incidence is higher e. Microscopic Orbital Retinoblastoma
(40%, 19 of 43) in Nepal, with proptosis being the most common
clinical manifestation of retinoblastoma.54 In several instances, orbital extension of retinoblastoma may not
be clinically evident and may only be microscopic. Detection of
Clinical Manifestations full-thickness scleral infiltration, extrascleral extension and invasion
of the optic nerve on histopathologic evaluation of an eye
There are several clinical presentations of orbital retinoblastoma. enucleated for intraocular retinoblastoma are unequivocal features
of orbital retinoblastoma. Tumor cells in choroidal and scleral
a. Primary Orbital Retinoblastoma emissaria and optic nerve sheath indicate possible orbital extension
mandating further serial sections and detailed histopathologic
Primary orbital retinoblastoma refers to clinical or radiologically analysis.
detected orbital extension of an intraocular retinoblastoma at the
initial clinical presentation, with or without proptosis or a fungating Diagnostic Evaluation
mass (Figure 32). Silent proptosis without significant orbital and
periocular inflammation in a patient with manifest intraocular A thorough clinical evaluation paying attention to the subtle signs
tumor is the characteristic presentation. Proptosis with of orbital retinoblastoma is necessary. Magnetic resonance imaging
inflammation generally indicates reactive sterile orbital cellulitis preferably, or computed tomography scan of the orbit and brain
secondary to intraocular tumor necrosis. in axial and coronal orientation with 2-mm slice thickness helps
confirm the presence of orbital retinoblastoma and determine its
b. Secondary Orbital Retinoblastoma extent. Systemic evaluation, including a detailed physical
examination, palpation of the regional lymph nodes and fine needle
Orbital recurrence following uncomplicated enucleation for aspiration biopsy if involved, imaging of the orbit and brain, chest
intraocular retinoblastoma is named secondary orbital x-ray, ultrasonography of the abdomen, bone marrow biopsy and
retinoblastoma (Figure 33). Unexplained displacement, bulge or cerebrospinal fluid cytology are necessary to stage the disease.
extrusion of a previously well-fitting conformer or a prosthesis is Technetium-99 bone scan and positron-emission tomography
an ominous finding suggestive of orbital recurrence. coupled with computed tomography may be useful modalities of
the early detection of subclinical systemic metastases. Orbital
c. Accidental Orbital Retinoblastoma biopsy is rarely required, and should be considered specifically
when a child presents with an orbital mass following enucleation
Inadvertent perforation, fine-needle aspiration biopsy or or evisceration where the primary histopathology is unavailable.
intraocular surgery in an eye with unsuspected intraocular
retinoblastoma should be considered as accidental orbital Management of Orbital Retinoblastoma
retinoblastoma and managed as such (Figure 34).
Primary orbital retinoblastoma has been managed in the past with
d. Overt Orbital Retinoblastoma orbital exenteration, chemotherapy or external beam radiotherapy
in isolation or in sequential combination with variable results.55-60
Previously unrecognized extrascleral or optic nerve extension It is well known that local treatments have a limited effect on the
discovered during enucleation qualifies as overt orbital course of this advanced disease. Orbital exenteration alone is
retinoblastoma. Pale pink to cherry red episcleral nodule, generally unlikely to achieve complete surgical clearance and preclude
in juxtapapillary location or at the site of vortex veins, may be
visualized during enucleation. An enlarged and inelastic optic nerve

56 DOS Times - Vol. 13, No.4, October 2007

to triple-freeze-thaw cryotherapy and enucleation should be
performed at the earliest possible convenience. Histopathologic
evaluation of such eyes may include specific analysis of the sites of
sclerotomy ports or the cataract wound for tumor cells.

If an extraocular extension is macroscopically visualized during
enucleation, special precaution is taken to excise it completely along
with the eyeball, preferably along with the layer of Tenon’s capsule
intact in the involved area. 11

All patients with accidental, overt or microscopic orbital
retinoblastoma undergo baseline systemic evaluation to rule out
metastasis. Orbital external beam radiotherapy (fractionated 45-
50 Gy) and 12 cycles of high dose chemotherapy is recommended.16

Metastatic Retinoblastoma

Figure 35. A child with primary orbital retinoblastoma Metastatic disease at the time of retinoblastoma diagnosis is very
(top left), showing massive orbital tumor on computed rare. Therefore, staging procedures such as bone scans, lumbar
tomography scan (top right). Following 12 cycles of high-dose puncture, and bone marrow aspirations at the initial presentation
chemotherapy, extended enucleation and orbital external are generally not recommended. The common sites for local spread
beam radiotherapy (bottom left). The child is alive and well and metastasis include orbital and regional lymph node extension,
and wears a custom ocular prosthesis 3 years following central nervous system metastasis, and systemic metastasis to bone
and bone marrow. Metastasis in retinoblastoma usually occurs
completion of treatment (bottom right). within one year of diagnosis of the retinoblastoma. If there is no
metastatic disease within 5 years of retinoblastoma diagnosis, the
child is usually considered cured.

secondary relapses; external beam radiotherapy does not generally Metastatic retinoblastoma is reported to develop in fewer than
prevent systemic metastasis; and chemotherapy alone may not 10% of patients in advanced countries. However, it is a major
eradicate residual orbital disease. 55-60 Therefore, a combination contributor to retinoblastoma related mortality in developing
therapy is considered to be more effective. We have developed a nations. Until recently, the prognosis with metastatic
treatment protocol comprising of initial three drug (Vincristine, retinoblastoma was poor. Conventional dose chemotherapy using
Etoposide, Carboplatin) high dose chemotherapy (3-6 cycles) vincristine, doxorubicin, cyclophosphamide, cisplatin, and
followed by surgery (enucleation, extended enucleation or orbital etoposide combined with radiation therapy has yielded only a few
exenteration as appropriate), orbital radiotherapy, and additional survivors. Dismal results with conventional therapy has prompted
12 cycle standard dose chemotherapy.17 In 6 carefully selected the use of high dose chemotherapy with hematopoietic stem cell
cases without intracranial extension and systemic metastasis, there rescue. Twenty-five patients with extra ocular disease or invasion
was dramatic resolution of orbital involvement. All the involved of the cut end of optic nerve received high-dose chemotherapy
eyes became phthisical after 3 cycles of high dose chemotherapy. including carboplatin, etoposide, and cyclophosphamide followed
No clinically apparent orbital tumor was found during enucleation. by autologous hematopoietic stem cell rescue. The three year
All patients completed the treatment protocol of orbital external disease-free survival was 67%. 60,61 All except one patient with
beam radiotherapy, and additional 12 cycle standard central nervous system disease died. The main side effects were
chemotherapy. All the patients were free of local recurrence or hematological, mucositis, diarrhoea, ototoxicity, and cardiac
systemic metastasis at a mean follow-up of 36 months (range 12- toxicity. Overall the response rate suggested that the treatment
102 months) and achieved acceptable cosmetic outcome regimen was promising in patients with bone or bone marrow
(Figure 35). 17 involvement, but not in patients with central nervous system
disease.
Our treatment protocol outlined for primary orbital
retinoblastoma is currently under evaluation for secondary orbital Children’s Oncology Group will be conducting a trial for the
retinoblastoma and early results have been very encouraging. treatment of metastasis retinoblastoma. In this trial, the patients
Surgical intervention in such cases may be limited to excision of will be stratified into 3 groups: orbital/nodal disease, central nervous
the residual orbital mass or an orbital exenteration depending on system disease, and systemic disease. Each patient will undergo
the extent of the residual tumor after the initial 3-6 cycles of high- induction therapy with cisplatin, cyclophosphamide, vincristine,
dose chemotherapy. and etoposide. Those with systemic metastasis or central nervous
system disease will then receive high dose therapy with etoposide,
All eyes that have undergone an intraocular surgery for carboplatin and thiotepa. The chemotherapy protocol will be
unsuspected retinoblastoma should be promptly enucleated. 16 changed as preliminary data with other agents becomes available.
Conjunctiva overlying the ports with about 4 mm clear margins
should be included en-bloc with enucleation. Random orbital Conclusion
biopsy may be also obtained, but there is no data to support its
utility. If immediate enucleation is not logistically possible, then There has been a dramatic change in the overall management of
the vitrectomy ports or the surgical incision should be subjected retinoblastoma in the last decade. Specific genetic protocols have

www.dosonline.org 57

been able to make prenatal diagnosis of retinoblastoma. Early 14. Honavar SG, Rajeev B. Needle Tract Tumor Cell Seeding Following
diagnosis and advancements in focal therapy have resulted in Fine Needle Aspiration Biopsy for Retinoblastoma. Investigative
improved eye and vision salvage. Chemoreduction has become Ophthalmology and Visual Science 1998; 39: S 658.
the standard of care for the management of moderately advanced
intraocular retinoblastoma. Periocular chemotherapy is now an 15. Honavar SG, Shields CL, Shields JA, Demirci H, Naduvilath TJ.
additional useful tool in salvaging eyes with vitreous seeds. Intraocular surgery after treatment of retinoblastoma. Arch
Enucleation continues to be the preferred primary treatment Ophthalmol. 2001;119:1613-21.
approach in unilateral advanced retinoblastoma. Post-enucelation
protocol, including identification of histopathologic high-risk 16. Shields CL, Honavar S, Shields JA, Demirci H, Meadows AT.
characteristics and provision of adjuvant therapy has resulted in Vitrectomy in eyes with unsuspected retinoblastoma.
substantial reduction in the incidence of systemic metastasis. The Ophthalmology. 2000;107:2250-5.
vexing orbital retinoblastoma now seems to have a cure finally
with the aggressive multimodal approach. Future holds promise 17. Honavar SG, Reddy VAP, Murthy R, Naik M, Vemuganti GK.
for further advancement in focal therapy and targeted drug Management of orbital retinoblastoma. XI International Congress
delivery. of Ocular Oncology. Hyderabad, India, 2004. pp. 51.

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Author
Santosh G. Honavar MD, FACS

www.dosonline.org 59

Analyzing Disc Edema Neurophthalmology

Rohit Saxena MD, Munish Dhawan MD

Optic disc and the retina are the only portions of the central There are 2 subtypes of AION. The first one is the arteritic variety,
nervous system that can be viewed during a clinical associated with giant cell arteritis (GCA). The second one is the
examination. Swelling of the disc is the only visible acute response more common nonarteritic variety, presumably solely due to
of the optic disc to most pathological processes that can damage it. atherosclerosis and occlusive small vessel disease.
The main causes of disc edema are increase in the intracranial
tension, inflammation and ischemia. Clinical Features

Patients with optic disc edema may present in a variety of ways • Unilateral, painless, moderate to severe loss of vision.
ranging from being asymptomatic (papilledema) to severe visual
loss (papillitis) depending upon the etiology of the nerve swelling. • Field defect is most commonly an inferior altitudinal defect.

Pathophysiology • Visual acuity ranges from 20/200 to no light perception.

Disc edema occurs due to stasis of the axoplasmic flow, or slowed • Age group affected is from middle-aged to elderly.
cellular conduction along the nerve. There is an obstruction to
flow at the level of the lamina cribrosa resulting in accumulation of • NAION is usually associated with systemic vascular disease
the intracellular fluids and metabolic by-products which collect at [hypertension (35-50% cases), diabetes (10-25%),
the level of the optic nerve head. Mechanical compression, atherosclerosis, blood coagulopathies, nocturnal hypotension)
infiltration, infection, inflammatory disease, demyelinating disease, or collagen vascular disease].
or compromised vascular perfusion to the nerve may all lead to
disc edema. • Arteritic AION is associated with GCA, in which the patient
may have associated signs of anorexia, weight loss, decreased
appetite, jaw claudication, scalp tenderness and malaise.

Causes of Unilateral optic disc edema

Hyperemic disc edema

• Papillitis
• Asymmetric papilledema (Figure 1)
• Compressive optic neuropathy
• Pseudopapilledema
• Others (uvietis, hypotony etc.)
Pale disc edema

• Anterior Ischemic Optic Neuropathy (AION)

Causes of Bilateral optic disc edema

• Papilledema (Figure 2)
• Hypertensive retinopathy ( Figure 3)
• Atypical optic neuritis
• Pseudopapilledema
• Compressive optic neuropathies
• Others (uveitis, infiltrative etc.)

Anterior Ischemic Optic Neuropathy

Anterior ischemic optic neuropathy (AION) is a general term
referring to all causes resulting in temporary or permanent
obstruction to the vascular flow. It presents with segmental or
diffuse pale disc edema.

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Figure 1. Asymmetric papilledema.
All India Institute of Medical Sciences, New Delhi
65
www.dosonline.org

Workup disc edema

Figure 2. Papilledema.

• Fundus picture shows focal or diffuse pale disc edema with • Embolic disease
flame shaped hemorrhages near the disc margins. (Figure 4)
• Migraine
Clinical setting in which ischemic optic neuropathy is seen are
• Sudden and severe hypotension
• Giant cell arteritis
• Collagen vascular diseases • Cardiac insufficiency
• Syphilis
• Herpes zoster • Patients on systemic therapy with certain drugs e.g.
• Arteriosclerosis amiodarone
• Diabetes mellitus
• Hypertension Pathophysiology

AION occours due to acute infarction of the short posterior ciliary
arteries supplying the anterior part of the optic nerve. In the non-
arteritic form, these vessels are compromised by vascular disease
and arteriolosclerosis. In the case of arteritic AION, these vessels,

66 DOS Times - Vol. 13, No.4, October 2007