|Year : 2000 | Volume
| Issue : 2 | Page : 101-6
Surgery for stage 5 retinopathy of prematurity: The learning curve and evolving technique
L Gopal, T Sharma, M Shanmugam, SS Badrinath, A Sharma, SG Agraharam, A Choudhary
Medical and Vision Research Foundation, Chennai, India
Medical and Vision Research Foundation, Chennai
Source of Support: None, Conflict of Interest: None
Purpose: To describe our experience with management of eyes with stage 5 retinopathy of prematurity (ROP)
Methods: Closed vitreoretinal surgery was done on 96 eyes of patients with stage 5 ROP. Lens was sacrificed in all but one eye. Surgery involved an attempt to clear all preretinal tissue and open the peripheral trough all round. In most instances bimanual surgery under viscoelastic was performed.
Results: At last follow up, anatomical success (defined as attached posterior pole) was achieved in 22.5% cases. Significant postoperative problems included reproliferation and secondary glaucoma. Only two infants obtained mobile vision.
Conclusion: Late identification of disease, lack of prior treatment such as laser or cryo, and higher incidence of narrow-narrow funnel configuration were responsible for the poor surgical results noted in this series. The poor surgical and functional results reemphasise the need for prompt screening and management of infants at risk.
Keywords: Clinical Competence, Comparative Study, Female, Humans, Infant, Infant, Newborn, Lens, Crystalline, surgery, Male, Ophthalmology,
|How to cite this article:|
Gopal L, Sharma T, Shanmugam M, Badrinath S S, Sharma A, Agraharam S G, Choudhary A. Surgery for stage 5 retinopathy of prematurity: The learning curve and evolving technique. Indian J Ophthalmol 2000;48:101
|How to cite this URL:|
Gopal L, Sharma T, Shanmugam M, Badrinath S S, Sharma A, Agraharam S G, Choudhary A. Surgery for stage 5 retinopathy of prematurity: The learning curve and evolving technique. Indian J Ophthalmol [serial online] 2000 [cited 2021 May 8];48:101. Available from: https://www.ijo.in/text.asp?2000/48/2/101/14895
With improved neonatal care that enables low birth-weight infants to survive, the incidence of retinopathy of prematurity (ROP) has increased in India. Unfortunately, there is no proportionate increase in awareness of this condition among neonatologists and ophthalmologists; thus not every child at risk of ROP is screened at the appropriate time. Threshold disease responds to cryotherapy and laser photocoagulation and can prevent progression to retinal detachment in a majority of cases.[1-4] However zone 1 disease (especially rush disease) can progress to retinal detachment despite treatment. Unrecognised zone 2 disease can also lead to retinal detachment. Surgical treatment is required at this stage. Scleral buckling has been recommended and is successful in stage 4 and some cases of stage 5 disease. However, most cases of ROP with retinal detachment that presented to us came at a stage when buckling was not possible. This article deals with our experience in the management of stage 5 ROP by closed vitreoretinal surgery.
| Materials and Methods|| |
This is a retrospective study of 96 eyes of 65 patients that underwent vitreoretinal surgery for stage 5 ROP at our institution over a period of 6 years (1992-98). There were 40 males and 25 females. The age at presentation to us varied from 2 to 16 months (mean, 5.9 months; median, 5 months). The mean birth weight was 1222.54 gms (SD 251.25) [Table - 1]. There were 11 patients weighing more than 1750 gms at birth and 2 patients who weighed more than 2000 gms at birth and yet developed stage 5 ROP. The mean gestational age was 28.78 weeks (S.D 5.41 weeks) [Table - 2].
Only 10 of the 96 eyes (10.4%) had threshold disease, had treatment with cryo or photocoagulation and yet progressed to stage 5. The rest (86 eyes) presented to the ophthalmologist with stage 5 ROP. Four of the 96 eyes had scleral buckling for stage 4 disease. Of the 65 patients, 31 had surgery in both eyes for a similar problem. The status of the fellow eye is given in [Table - 3]. The mean age at surgery was 7.4 months [Table - 4]. The apparent delay between presentation of the patient to us and the time of surgery was due to: (1) the time taken by the parents to decide on the surgery and (2) the fact that the surgery on the second eye (in bilateral cases) was usually done 4 weeks after the first eye. Thirteen of the infants were born as one of multiple births (twins). Significant anterior segment findings were presence of corneal haze in 6 eyes and 360ø posterior synechiae in 5 eyes. Although the basic goals of surgery were the same in all cases, the actual surgical procedure differed from case to case due to improvisations made from time to time and our learning curve.
| Surgical Procedure|| |
The surgery consisted of closed vitrectomy and the lens was sacrificed in all but one case. The sclerotomies were made 0.5 mm from the limbus, usually through or just behind the iris root A 30ø bent cannula was placed in the lens bag and the vitreous cutter was used to perform lensectomy. The anterior capsule was also removed. The posterior capsule was subsequently peeled off using an intraocular forceps.
| Management of the pupil|| |
Where the pupil was mobile, adrenaline in the infusion fluid (0.1 ml of 1:1000 dilution in 500 ml of infusion fluid) was able to keep it widely dilated. However, in most cases the pupil was bound down at one or more places and did not permit adequate dilation. In an attempt to get maximum pupillary aperture, temporary iris retractors (Greishaber, Switzerland) were used. In most cases, however, the iris was sacrificed in the meridian of the sclerotomies and this not only offered good visualisation of the periphery but avoided the iris prolapse that tended to occur frequently through the sclerotomies. We realised that the superior 2-3 clock hours of iris that was left in between did not have enough rigidity and tended to fall back and adhere to the peripheral retina. Hence, in the later cases we routinely excised this part of iris, leaving a large superior iris coloboma. Visualisation of the inferior periphery was facilitated by the use of two temporary iris retractors, scleral indentation, or both.
| Facilitation of bimanual surgery|| |
In initial cases we performed unimanual dissection using scissors in one hand and handheld infusion in the other. In bimanual surgery we tried using anterior chamber infusion using a broken butterfly needle. This, however, produced corneal oedema at the site of the infusion and the distortion caused by attempts to reach out to the periphery even caused damage to the endothelium by the infusion tip. Subsequently, bimanual surgery was done using the curved vitreous scissors (DORC, Holland) and pic forceps (Greishaber, Switzerland) under viscoelastic fill of the eye [sodium hyaluronate (Biolon;TM Nirans, India) or methyl cellulose (Viscomet,TM Milmet, India) [Figure - 1] and [Figure - 2]. Any leak of the viscoelastic during dissection was made good by intermittent injection of the same. No indwelling catheter was placed for this purpose.
| Initiation of dissection|| |
The initiation and progress of dissection underwent changes as we gained experience. In the first part of this series, we initiated the dissection by making a cut at the opening of the funnel using a disposable needle. The cut was made to incise all the layers up to the retinal surface; radial cuts were then made with scissors in several meridians. The general dissection proceeded from the centre to the periphery. Very often, the extreme anterior portion was difficult to dissect, leading to unopened trough at places. In a pilot study we used the temporary iris retractors to provide a wide pupillary aperture and initiated the dissection from the periphery to the centre. As a first step the fibrovascular tissue was dissected from the ciliary processes all round, then onwards along the plateau of retina and into the funnel. Once the 360ø dissection was made in the periphery, dissecting posteriorly was relatively easy, more complete and did not leave behind any membranes on the retina. This procedure was possible in those cases with a broad trough. We realised that we could not adopt this technique successfully in all cases.
Currently we use a combination of the above described techniques. The initial cut is made in the centre with a needle. The radial cuts are then made preferably in the meridians of the sclerotomies all the way up to the periphery. The anterior limits of the cuts are used as handles for dissection circumferentially 360ø to cut the tissue from the ciliary processes. The dissection then proceeded posteriorly.
| Posterior dissection|| |
Once the peripheral cut was made the tissue was dissected into the funnel. As a first step the tissue was dissected off the plateau of the retina. Coaxial illumination of the microscope was used for the dissection into the funnel. The blades of the scissors were kept vertically, parallel to the walls of the funnel. Injecting viscoelastic into the funnel helped in visualisation.
En bloc removal of all tissue is possible by using this periphery-to-centre dissection. Minimal ooze from the retinal surface usually stopped spontaneously. Blood collected at the site of dissection could also be displaced by injecting viscoelastic at that site. If significant blood had collected, infusion was used to remove the blood and the viscoelastic; and bipolar endocautery was used to cauterize the bleeders. Viscoelastic was reinjected and the dissection was continued. In general, no attempt was made to drain the subretinal fluid (SRF). In one case we tried to drain the SRF externally while injecting perfluorocarbon liquids (PFCL) into the vitreous cavity in an attempt to settle the retina intraoperatively to some extent. This approach was not successful.
| Lens sparing vitrectomy|| |
Lens sparing vitrectomy was done only in one eye with zone 1 disease that had received extensive laser and cryo and yet developed posterior pole retinal detachment. The fibrovascular tissue could be dissected with unimanual surgery under viscoelastic using the scissors and light pipe. The tissue was dissected up to the ridge. The anterior attached retina had a fibrillary vitreous-like structure adherent to it but fibrosis was absent.
| Resurgery|| |
In 9 eyes (including the eye in which lens-sparing vitrectomy was done), resurgery for additional membrane dissection was done. Resurgery was attempted only in cases of limited reproliferation where the retina had receded to some extent but did not reattach. The procedure involved surgery under viscoelastic using bimannal dissection. In the eye with initial lens-sparing vitrectomy, the lens was sacrificed during the resurgery. At this time it was detected that the fibrosis had extended on to the attached retina.
| Complications|| |
Retinal dialysis occurred in 14 eyes (14.6%). In 2 eyes, the dialysis was visualized but in the rest the presence of dialysis was inferred from the observation of entry of subretinal fluid into the vitreous cavity (schleiren). This was easy to identify when the subretinal fluid contained cholesterol crystals or flakes of altered blood. A posterior retinal break occurred in 3 eyes (3.1%). The surgery could not be completed in 3 eyes (3.1%) because of extensive bleeding. The exact incidence of altered blood in subretinal space was not available from the charts, but it was probably seen in about 60% of the cases. There were no anaesthesia-related problems.
| Results|| |
Most surgeons consider posterior polar reattachment as anatomical success in cases of surgery for stage 5 ROP. The retinal status at 2 months? visit and the last follow up is given in [Table - 5]. One infant was lost to follow up 7 days after the surgery. Fourteen of the eyes seen at the 2 months? visit were subsequently lost to follow up. All these were eyes with anatomical failure. The remaining infants had a follow up between 3 and 72 months. The mean follow up of the eyes with attached retina was 14 months and those with posterior polar reattachment was 15.85 months. A few cases that had shallow retinal detachment at 2 months were subsequently reattached. Two eyes had total redetachment though attached initially at the 2 months? visit. One of these had total redetachment 8 months later (2 months after cyclophotocoagulation). A large hole developed in the macula in each of these eyes.
Postoperative intense vitritis was noted in most of the cases in the first postoperative day, but cleared within a few days with hourly topical steroid instillation. Transient high IOP and corneal oedema were relatively uncommon, but were seen when significant amounts of viscoelastic were left behind. Hence we routinely irrigated the viscoelastic before closure of the sclerotomies. To avoid the hypotony that may occur while closing the sclerotomies, we used preplaced 8-0 vicryl shoelace sutures. The sutures were pulled tight by the assistant while the instruments were withdrawn. This also avoids any bleeding that can occur due to hypotony.
At last follow up a total of 22.9% had anatomical success, of which only 10.4% had total attachment of the retina [Figure - 3]. Nearly half of the cases (54.2%) had highly elevated total retinal detachment at the last visit. In most of these cases there was severe reproliferation and the retina was very often seen adherent to the back of the iris. The relation between anatomical success and configuration of the funnel is given in [Table - 6]. Ten eyes developed secondary glaucoma in the postoperative period of which 6 eyes had attached retina (two with total retinal reattachment and four with posterior polar reattachment). Trabeculectomy was done in two eyes, both of which developed large staphylomas at the sites of trabeculectomy. Hence subsequent cases were managed with trans scleral diode laser cyclophotocoagulation, if the medical treatment with betablockers was insufficient to control the intraocular pressure (IOP).
The visual acuity in these infants was very difficult to judge. Fix-and-follow behaviour was not seen consistently in eyes with attached retina; while surprisingly, a few infants with shallow retinal detachments had fix-and-follow behaviour. Only two children showed mobile vision. One child could walk without stumbling into objects, although it was difficult to elicit even finger counting vision. Part of the problem was due to delayed developmental milestones, which were not uncommon.
| Discussion|| |
The surgical approaches and algorithms applicable to the adult retinal detachments do not apply in stage 5 ROP surgeries. The initial attempts were made by Triester and Machemer in 1977. It was rapidly realised that entry through pars plana was not suitable, since it led to subretinal entry of instruments. Entry through the limbus or pars ciliaris was more suitable. For successful surgery it is important to understand the anatomy of an eye with ROP. The fibrovascular tissue starts at the ridge (junction of the vascularised and nonvascularised portion of the retina). The vascularised posterior retina gets detached and stretched, while the avascular peripheral retina remains attached. This leads to a peripheral trough of variable width. Subsequently the fibrosis spreads to the surface of the posterior vascularised retina and also bridges across the trough upto the ciliary processes.
The absence of definable pars plana and the presence of fibrous tissue near the ciliary processes makes it imperative that the entry of the instruments be anterior to the ciliary processes. Currently there are two approaches: open sky vitrectomy and closed vitrectomy. The presumed advantages of the open sky approach are the ability to dissect the periphery better and the ability to remove the tissue en bloc. The disadvantages are the need for additional surgery such as suturing of the corneal button; prolonged hypotony with attendant risk of choroidal detachment; and relative difficulty in dissecting near the posterior pole. Due to its familiarity, closed vitrectomy has been the most popular approach with most vitreoretinal surgeons.
The most important disadvantage of this approach is the relatively difficult access to the periphery, leading to less-than-satisfactory relief of the peripheral traction. We attempted several modifications to overcome these limitations.
The first obstacle was the limited vascularisation of the periphery. Temporary iris retractors in four quadrants was used in a pilot study. However, we soon realised that due to reasons already mentioned, creating a superior iris coloboma gives good visualisation of superior periphery.
In our experience, bimanual surgery under viscoelastic is perhaps the best approach to dissection. The curved scissors and the pic forceps were used for both peripheral and posterior dissection. We also found that dissecting from periphery to the centre is better than the other way round. However, beginning the dissection in the periphery was not always possible unlike in the open-sky approach, except in cases with a broad peripheral trough. Hence we used the peripheral limits of radial cuts made from a central incision as starting points to create a circumferential cut close to the ciliary processes. Successful completion of this circumferential cut leads to the retina falling back and unravels the true dimension of the trough.
Bleeding was not a major problem in most cases. The ooze could be displaced with an injection of viscoelastic permitting completion of the dissection. A complete washout and refill with viscoelastic was usually required only 2-3 times during the entire procedure. Bleeding occurred more commonly in eyes of infants that were operated early (around 3-4 months), particularly when treatments such as photocoagulation or cryopexy were not done previously. Retinal dialysis was noted in 14 eyes. Dialysis seemed to occur usually while trying to dissect in the periphery. During bimanual dissection, one may exert extra traction on the periphery and produce dialysis. This can be avoided by using scleral depression in a relatively hypotonous eye. Posterior retinal breaks were less common (three eyes). The short blades of the curved scissors permitted safe dissection in the confines of the narrow funnel aided by injection of viscoelastic into the funnel in small quantities. Iatragenic retinal break posteriorly is sure to lead to failure of surgery.
SRF drainage was not attempted in most of our cases. The retina was seen to remain stiff intraoperatively despite relief of traction. The general contour of the folds was retained, unlike in adult retinal detachments. Forcing such a retina against the retinal pigment epithelium with fluid-air exchange has a high risk of retinal break formation. In the absence of retinal break and reproliferation, the retina gets spontaneously reattached in 4-6 weeks. Use of PFCL and simultaneous drainage of SRF in surgery for stage 5 ROP was described by Deveny. This technique did not work in our hands. The PFCL failed to flatten the stiff retina, and instead migrated into the recesses of the peripheral trough, from where it was difficult to extricate in the absence of a third port.
Trese et al have recently emphasised the need for early recognition and management to achieve better results. In their series the mean birth weight was 784 gms, gestational age 25.5 weeks and average age at surgery for stage 4 and 5 ROP 4.5 months. Comparatively in our series the mean birth weight, gestational age and average age at surgery were 1222.5 gms, 28.8 weeks and 7.4 months respectively. About 86% of cases that presented to us had no prior treatment. These factors probably define the surgical anatomy of the eyes in this series of patients. Obviously lack of routine screening programmes in India have lead to larger babies and eyes with anterior zone 2 disease developing retinal detachments. Unlike posterior zone 2 and zone 1 disease, these eyes are likely to have shallower and narrower troughs which makes dissection in the periphery difficult. In this tudy, 81.3% eyes had narrow-narrow configuration of the funnel in comparison to 28.8% seen in a study by Jabbour et al. Narrow-narrow configuration of the funnel is known to be associated with poor anatomical results (19% success in narrow funnel versus 81% success in open funnel).
The visual results have been unsatisfactory despite surgical reattachment of the retina in ROP.[l6] Factors that potentially could influence the visual results are the duration of retinal detachment and presence of significant of amounts subretinal blood [Figure - 4]. However, we found visual results to be equally disappointing even in cases where retina was attached in early postoperative period (four months postnatally). Detached retina in a growing premature infant seems to undergo permanent degenerative changes, much more than an adult retina detached for a similar duration. The striking feature of even reattached retina is its obviously thin texture. Over a period of time, this seems to become progressively thinner and has usually variable pigmentation similar to spontaneous reattachment of adult retina. Recurrent retinal detachment long after successful reattachment was also unique with ROP. The retina does not seem to grow with the growing eyeball; it is stretched thin, thus giving way at vulnerable points such as the macula leading to recurrent retinal detachment even in the absence of significant reproliferation.
In our series of patients secondary glaucoma occurred preferentially in eyes with attached retina (25% versus 5.6%). This probably can be explained by the effect on IOP of persistent retinal detachment, as well as altered ciliary body function secondary to recurrent proliferation that exerts traction on the ciliary body. The high incidence of glaucoma in eyes with surgical success further vitiates the environment for rehabilitation of the child. The trabecular meshwork in the ROP eyes could also be abnormal, further increasing the risk of glaucoma despite absence of peripheral anterior synechiae. Treatment of the secondary glaucoma can be as frustrating as the retinal detachment itself. Invasive procedures are best avoided due to the high risk of staphyloma at the site of glaucoma surgery. Cyclophotocoagulation is probably a better option. Where second surgery is contemplated for limited reproliferation, endo-cyclophotocoagulation can be done along with the revitrectomy, for management of coexisting secondary glaucoma.
Understanding why the retina remains stiff and does not lend itself to reattachment during surgery and identification of growth factors that can give normal texture to the attached retina, may improve the surgical success in stage 5 ROP. In the Indian scenario, mandatory screening by trained ophthalmologists of infants at risk will go a long way in reducing the needless progression of the disease to stage 5 in the larger babies and also in making stage 5 ROP surgery more successful.
| References|| |
Cryotherapy for retinopathy of prematurity cooperative group - Multicentre trial of cryo therapy for retinopathy of prematurity. Preliminary results. Arch Ophthalmol
Cryotherapy for retinopathy of prematurity comparative group - Multicentre trial of cryo therapy for retinopathy of prematurity, one year outcome - structure and function. Arch Ophthalmol
Nagata M, Kobayashi Y, Fukuda M, Suckawe K. Photocoagulation for treatment of retinopathy of prematurity. Jap J Clinical Ophthalmol
Deshpande DA, Chaturvedi M, Gopal L, Ramachandran S, Shanmuga Sundaram RS. Treatment of threshold ROP. Indian J Ophthalmol
Orellana J. Scleral buckling in acute ROP stages in treatment of ROP. In Eichenbaum JW, Mamolok A, Mittl KN, Orellana J, editors. Yearbook.
Chicago: Medical Publishers Inc; 1990. pp 194-211.
Gopal L, Sharma T. Periphery to centre dissection for stage V retinopathy of prematurity aided by temporary iris retractors-a pilot study. Hong Kong J Ophthalmol
dejuan E Jr, Machemer R, Charles ST, Hirose T, Tasman WS, Trese MT. Surgery for stage 5 ROP (letter). Arch Ophthalmol
Treister G, Machemer R. Results of vitrectomy for rare proliferative and hemorrhagic diseases. Am J Ophthalmol
dejuan E Jr, Machemer R, Retinopathy of prematurity - Surgical technique. Retina
Hirose T. Surgery for stage 5 ROP. Flynn JT, Tasman W, editors. ROP-A Clinician?s Guide.
New York: Springer Verlag. 1992.pp 95-114.
dejuan E Jr, Machemer R, Flynn JT, Green WR. Surgical pathoanatomy in stage 5 ROP. Flynn JT, Phelps PL, (editors). ROP: Problems and Challenges.
New York: Alan Bliss Inc: 1988. pp 281-86.
Deveny RG. Perfluorocarbon liquid as a surgical adjunct in the surgical repair of stage V retinopathy of prematurity (letter). Br J Ophthalmol
Trese MT, Droste PJ. Long term post operative results of a consecutive series of stage 4 and 5 retinopathy of prematurity. Ophthalmology
Gopal L, Sharma T, Ramachandran S, Shanmuga Sundaram R. Retinopathy of prematurity:A study. Indian J Ophthalmol
Jabbour NM, Eller AE, Hirose T, Schepens CL, Liberfarb R. Stage 5 ROP. prognostic value of morphologic findings. Ophthalmology
Charg LP, Machemer R, dejuan E Jr. Vitrectomy for advanced stage of ROP. Am J Ophthalmol
Trese MT. Visual results and prognostic factors of vision following surgery for stage V ROP. Ophthalmology
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]
|This article has been cited by|
||Anatomical and visual outcome of stages 4 and 5 retinopathy of prematurity
| ||Shah, P.K., Narendran, V., Kalpana, N., Tawansy, K.A. |
| ||Eye. 2009; 23(1): 176-180 |
||Retinopathy of prematurity in South Africa: An assessment of needs, resources and requirements for screening programmes
| ||Varughese, S., Gilbert, C., Pieper, C., Cook, C. |
| ||British Journal of Ophthalmology. 2008; 92(7): 879-882 |
||Retinopathy of prematurity | [Prematüre retinopatisi]
| ||Ümit Sarici, S., Mehmet Mutlu, F., Ibrahim Altinsoy, H. |
| ||Cocuk Sagligi ve Hastaliklari Dergisi. 2008; 51(1): 51-61 |
||Plasmin enzyme-assisted vitrectomy for primary and reoperated eyes with stage 5 retinopathy of prematurity
| ||Wu, W.-C., Drenser, K.A., Lai, M., Capone, A., Trese, M.T. |
| ||Retina. 2008; 28(3 Suppl): S75-S80 |
||Changing pattern of childhood blindness in Maharashtra, India
| ||Gogate, P., Deshpande, M., Sudrik, S., Taras, S., Kishore, H., Gilbert, C. |
| ||British Journal of Ophthalmology. 2007; 91(1): 8-12 |
||Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: Implications for screening programs
| ||Gilbert, C., Fielder, A., Gordillo, L., Quinn, G., Semiglia, R., Visintin, P., Zin, A. |
| ||Pediatrics. 2005; 115(5): e518-e525 |
||Fulminate retinopathy of prematurity - Clinical characteristics and laser outcome
| ||Shah, P.K., Narendran, V., Saravanan, V.R., Raghuram, A., Chattopadhyay, A., Kashyap, M., Morris, R.J., (...), Shah, V. |
| ||Indian Journal of Ophthalmology. 2005; 53(4): 261-265 |
||Retinopathy of prematurity
| ||Azad, R., Chandra, P. |
| ||Journal of the Indian Medical Association. 2005; 103(7): 370-372 |
||A systematic review of anatomical and visual function outcomes in preterm infants after scleral buckle and vitrectomy for retinal detachment
| ||Ertzbischoff, L.M. |
| ||Advances in Neonatal Care. 2004; 4(1): 10-19 |
||Retinopathy of prematurity - Screening and management
| ||Azad, R.V., Chandra, P. |
| ||Journal of the Indian Medical Association. 2003; 101(10): 593-596 |
||Does my child really need to wear these glasses? A review of retinopathy of prematurity and long-term outcomes
| ||Kuerschner, D.R. |
| ||Newborn and Infant Nursing Reviews. 2003; 3(3): 110-117 |
||Programme planning and screening strategy in retinopathy of prematurity
| ||Jalali, S., Anand, R., Kumar, H., Dogra, M.R., Azad, R., Gopal, L. |
| ||Indian Journal of Ophthalmology. 2003; 51(1): 89-99 |