Downloaded from http://bjo.bmj.com/ on November 15, 2016 - Published by group.bmj.com Clinical science surgery in chronic Stevens–Johnson syndrome: aspects and outcomes Purvasha Narang,1 Ashik Mohamed,2 Vikas Mittal,3 Virender S Sangwan1

▸ Additional material is ABSTRACT in these patients due to the potential risks published online only. To view Aim To assess the outcome of cataract surgery in involved.5 This study aims to highlight the appro- please visit the journal online – (http://dx.doi.org/10.1136/ patients with chronic sequelae of Stevens Johnson priate management of cataract and the outcomes of bjophthalmol-2015-308041). syndrome (SJS). cataract surgery in patients with the chronic seque- Methods Setting: Tertiary eye care centre in South lae of SJS. 1Tej Kohli Institute, L V Prasad Eye Institute, India. Design: Retrospective, non-comparative, Hyderabad, India consecutive, interventional case series. Study period: MATERIALS AND METHODS 2 Prof. Brien Holden Eye March 2003 to May 2014. Of the 1662 consecutive The approval of the Institutional Review Board was Research Centre, L V Prasad patients with SJS, 32 patients (40 eyes) with chronic Eye Institute, Hyderabad, India obtained and the study adhered to the tenets of the 3Cornea and Anterior Segment sequelae of SJS who underwent cataract surgery were Declaration of Helsinki. This was a retrospective, Services, Sanjivni Eye Care, included. The main outcome measures were best- non-comparative, consecutive, interventional case Ambala City, India corrected visual acuity (BCVA) and ocular surface series carried out at the L V Prasad Eye Institute, stabilisation. The visual acuity was expressed with Hyderabad, India. A total of 1662 patients were Correspondence to reference to the logMAR. Dr Virender S Sangwan, Tej diagnosed to have SJS during the study period Kohli Cornea Institute, L V Results The study included 12 men (37.5%) and 20 (March 2003 to May 2014). The systemic diagnosis Prasad Eye Institute, L V Prasad women (62.5%). 8 patients (25%) had bilateral cataract was confirmed by a physician on presentation. Marg, Banjara Hills, Hyderabad surgeries. The median preoperative BCVA was 1.61 (IQR, Among these, the medical records of all the 500034, Telangana, India; 0.80 to 2.78) (only perception of light in three eyes). The [email protected] patients with chronic sequelae of SJS (n=32) who median BCVA in the immediate postoperative period was underwent cataract surgery (40 eyes) were reviewed Received 27 October 2015 0.60 (IQR, 0.30 to 1.48) (perception of light in an eye) and included in the study (figure 1). Accepted 27 January 2016 which was significantly different from the preoperative A detailed history and complete ophthalmic Published Online First BCVA (p<0.0001). The median BCVA achieved was 0.30 examination, including the results of fluorescein 22 February 2016 (IQR, 0.00 to 0.80), suggesting further improvement. staining and Schirmer type 1 test, were recorded Median time taken to achieve this postoperatively was for each patient. The age at presentation, duration 1.5 months (IQR, 8 days to 3 months). The median BCVA of disease, duration of diminution of vision, best- during the last follow-up was 0.48 (IQR, 0.18 to 1.00). corrected visual acuity (BCVA) at presentation, type The preferred type of cataract surgery was of cataract surgery done and its outcomes were phacoemulsification. Ocular surface condition remained noted. The main outcome measures were BCVA stable in 35 eyes (87.5%). Ocular surface breakdown in and stability of the ocular surface. The logMAR to four eyes (10%) was managed appropriately. Snellen equivalent visual acuity conversion (and Conclusion Cataract surgery outcome can be visually vice versa) was based on the published visual acuity rewarding in chronic sequelae of SJS provided ocular conversion chart.6 surface integrity is adequately maintained preoperatively The statistical analysis was done using the soft- and postoperatively. ware Origin (V.7.0; OriginLab Corporation, Northampton, Massachusetts, USA) and STATA (V.11.0; StataCorp, College Station, Texas, USA). INTRODUCTION The normality of the continuous data was assessed Stevens–Johnson syndrome (SJS) is a complex using the Shapiro–Wilk test. Mean and SD were immunological syndrome characterised by an acute used to describe the data with normal distribution, blistering affecting the skin and at least two whereas median and IQR were used for description mucous membranes.1 In the eye, it can present of data whose distributions were not normal. The with acute and chronic manifestations.2 Chronic Levene’s test for equal variance was applied to ocular sequelae occur in up to 35% of patients.3 evaluate homoscedasticity in group-wise compari- Even if the cornea is not affected during the acute sons. The paired t test was used to compare the stage, severe loss of vision due to persistent and continuous parametric data (equal variance), prolonged conjunctival inflammation and ulcer- whereas Wilcoxon signed-rank test was used for ation, cicatricial complications of the lid margin non-parametric data and continuous parametric and the tarsus, corneal scarring and neovascularisa- data (unequal variance). A p value of <0.05 was tion can result.4 This can cause profound bilateral considered statistically significant. blindness if not managed in a timely and appropri- ate fashion. RESULTS Visual rehabilitation in such cases is centred on The study included 12 men (37.5%) and 20 To cite: Narang P, improvement in ocular surface health, contact women (62.5%). Eight patients (25%) had bilateral Mohamed A, Mittal V, et al. lenses and ocular surface prosthesis, cataract extrac- cataract surgeries. The median age of the patients Br J Ophthalmol tion, corneal transplantation and keratoprosthesis. at presentation was 49 years (IQR, 35 to 56 years). – 2016;100:1542 1546. Cataract surgery is often delayed or not attempted The median duration of SJS at presentation was

1542 Narang P, et al. Br J Ophthalmol 2016;100:1542–1546. doi:10.1136/bjophthalmol-2015-308041 Downloaded from http://bjo.bmj.com/ on November 15, 2016 - Published by group.bmj.com Clinical science

median of 0.30 (IQR 0.00 to 0.80) (Snellen equivalent in feet: median 20/40, IQR 20/20 to 20/125), suggesting further visual improvement. The median time taken to achieve the best BCVA postoperatively was 1.5 months (IQR, 8 days to 3 months). The median BCVA during the last follow-up was 0.48 (IQR, 0.18 to 1.00) (Snellen equivalent in feet: median 20/60, IQR 20/30 to 20/200). Figure 2 shows the BCVA during the different visits.

Preoperative considerations Table 1 shows the various manifestations of chronic sequelae of SJS preoperatively. Figure 1 Digital photograph showing the ocular surface in The various medical and surgical procedures carried out to Stevens–Johnson syndrome where cataract surgery was still successfully stabilise the ocular surface before cataract surgery were punctal performed. cauterisation or plugs, preservative-free lubricants, topical ster- oids, ciclosporin eye drops (0.05%), amniotic membrane graft- ing (AMG), application of tissue adhesive with bandage contact 2.5 years (IQR, 4 months to 10 years). The median duration , tarsorrhaphy, symblepharon release, lid margin mucous between diagnosis of SJS and cataract surgery was 5.5 years membrane grafting (MMG), prosthetic replacement of the (IQR, 2 to 17 years). ocular surface ecosystem (PROSE), correction, lash epilation or electrocauterisation and dacryocystectomy. Three Visual outcomes eyes (7.5%), which presented in the acute stage of SJS, under- The analysis of BCVA on presentation revealed that five eyes went AMG in the initial treatment phase. The types of cataract (12.5%) had perception of light (PL+) with accurate projection observed in patients with SJS are described in table 2. of rays. For the rest of the eyes, the median BCVA in logMAR Posterior segment was evaluated using indirect ophthalmos- was 1.31 (IQR, 0.48 to 1.79) (Snellen equivalent in feet: copy and ocular ultrasonography B-scan was performed wher- median Counting Fingers (CF) 3 m, IQR 20/60 to CF 1 m). ever media opacity precluded examination. For the calculation Twenty-four eyes (60%) had BCVA less than 20/200 on presen- of intraocular lens (IOL) power, the keratometry values could tation. The median preoperative BCVA was 1.61 (IQR, 0.80 to be obtained for 17 eyes (42.5%), whereas average K-value of 2.78) (Snellen equivalent in feet: median CF 1.5 m, IQR 20/125 44.0 D was assigned to cases where corneal condition precluded to CF Close to Face) (PL+ in three eyes). There was a significant the acquisition of a reliable keratometric value. difference between the BCVA at presentation and the preopera- tive BCVA (p=0.006). Operative considerations The median BCVA in the immediate postoperative period was Local anaesthesia in the form of peribulbar block was adminis- 0.60 (IQR, 0.30 to 1.48) (Snellen equivalent in feet: median 20/ tered in 37 eyes (92.5%) undergoing cataract surgery, whereas 80, IQR 20/40 to CF 2 m) (PL+ in an eye) which was signifi- two eyes (5%) were operated under topical anaesthesia with cantly different from the preoperative BCVA (p<0.0001). All proparacaine (0.5%) and one eye (2.5%) required general patient’s visual acuity improved with the exception of one anaesthesia. patient in whom a vitreous haemorrhage was suspected in the Extracapsular cataract surgery (ECCE) was carried out in nine preoperative ultrasonography B-scan and the BCVA dropped eyes (22.5%), small incision cataract surgery (SICS) in five eyes from CF close to face to perception of hand movements close (12.5%) and phacoemulsification in 26 eyes (65%). ECCE was to face. On subsequent follow-up, the BCVA achieved was a performed through a posterior limbal incision with limited con- junctival dissection. It was preferred when central and superior corneal scarring was advanced. Wound closure was achieved by conventional interrupted 10–0 nylon sutures. SICS was also done with limited conjunctival dissection and superior scleral tunnel, especially in cases of peripheral corneal thinning.

Table 1 Preoperative manifestations of the chronic sequelae of Stevens–Johnson syndrome Preoperative ocular surface No. of eyes Proportion (%)

Obliteration of meibomian gland orifices 34 85 Symblepharon 32 80 Vascularized corneal scar 30 75 Lid margin keratinisation 29 72.5 Superficial punctate keratopathy 23 57.5 or distichiasis 15 37.5 Figure 2 Boxplot of best-corrected visual acuity (BCVA) (logMAR) in patients with Stevens–Johnson syndrome undergoing cataract surgery. Adherent leucoma 3 7.5 Pre-Op, preoperative BCVA; Post-Op Immediate, immediate Entropion 3 7.5 postoperative BCVA (ie, on day 1 postoperatively); Post-Op Max, Ankyloblepharon 2 5 maximum achieved BCVA during the postoperative period; Post-Op Fornix foreshortening 2 5 Last, BCVA on the last follow-up visit.

Narang P, et al. Br J Ophthalmol 2016;100:1542–1546. doi:10.1136/bjophthalmol-2015-308041 1543 Downloaded from http://bjo.bmj.com/ on November 15, 2016 - Published by group.bmj.com Clinical science

The adjunct procedures carried out with the cataract surgeries Table 2 Types of cataract in Stevens–Johnson syndrome were optical iridectomy (three eyes), tarsorrhaphy release (one Types of cataract No. of eyes Percentage eye) and conjunctival biopsy (two eyes) to rule out other causes of ocular surface cicatrisation. Total cataract 6 15 – Nuclear sclerosis grades 3 4 11 27.5 Postoperative considerations Nuclear sclerosis grades 1–2 7 17.5 The postoperative treatment regimen consisted of topical corti- Posterior subcapsular or posterior polar cataract 14 35 costeroids in the form of prednisolone acetate (1%) eye drops, Cortical cataract 2 5 six to eight times a day, a broad spectrum antibiotic-like moxi- floxacin hydrochloride (0.5%) four times a day, tear substitutes and cycloplegic eye drops (if necessary). Four eyes were treated Viscoexpression was performed for nucleus delivery. Where with topical ciclosporin drops (0.05%) prior to cataract surgery corneal clarity was reasonably preserved, either a scleral or clear and these were continued postoperatively. Similarly, use of sys- corneal tunnel phacoemulsification was performed using low temic immunosuppressants like oral methotrexate and corticos- aspiration parameter settings. The preferred technique for doing teroids in two patients was continued in the postoperative phacoemulsification was the stop-and-chop technique in 21 eyes period for ocular surface stabilisation. (80.7%) followed by direct chop in two cases (7.7%) and The common symptoms reported postoperatively were photo- divide-and-conquer in one case (3.9%). Irrigation and aspiration phobia (25.0%) and mild pain in the eye (7.5%). Ocular surface mode was solely used for two eyes (7.7%). condition remained stable in 35 eyes (87.5%) after the surgery. The anterior capsule of lens was stained using Trypan blue There was no evidence of corneal perforation, exaggerated con- fl dye (0.06 mg/mL) in 24 eyes (60%) for better visualisation and junctival in ammation or extensive symblepharon formation fol- 16 eyes (40%) did not require capsular staining. Continuous lowing cataract surgery. The ocular surface breakdown was seen curvilinear capsulorrhexis (CCC) was performed in 32 eyes in four eyes (10%). These eyes had a stable ocular surface pre- fi (80%), can-opener technique in four cases (10%), where operatively. One eye developed lamentary keratopathy and was corneal visibility precluded a CCC, and envelope technique in prescribed copious preservative-free lubricants. Two eyes four eyes (10%), where the anterior lens capsule was calcified. showed persistent corneal epithelial defects and were managed In-the-bag posterior chamber IOL placement was achieved in 36 using bandage contact lens and lubricants in one eye and AMG eyes (90%) and in-the-sulcus in one eye (2.5%). In two cases in the other eye along with tarsorrhaphy. Pseudomonal fi (5%) the IOL placement could not be determined due to hazy (con rmed on corneal scraping and culture) occurred in one eye fi view intraoperatively. One eye was left aphakic due to posterior (2.5%) and was successfully treated with forti ed antibacterials capsular rent and vitreous prolapse which was managed appro- with subsequent scar formation. Lid margin keratinisation con- priately. The most commonly used IOLs were foldable acrylic tinued to progress in few eyes and required lid MMG later. lenses in 28 eyes (70.0%) followed by poly(methyl methacryl- Other progressing lid sequelae like entropion and trichiasis were ate) (PMMA) lenses in 11 eyes (27.5%). also dealt with appropriately. Of the irrigating solutions used, ringer lactate was used for Postoperative use of PROSE in 18 eyes (45%) further the majority, that is, 38 eyes (95.0%) and balanced salt solution improved unaided visual acuity as well as comfort in these was used for two eyes (5.0%). Hydroxypropylmethyl cellulose patients. The current practice is to permit the use of PROSE – 2% was used as the viscoelastic agent in 37 cases (92.5%), 4 5 weeks after cataract surgery, though the data on exact fi sodium hyaluronate 1% in two cases (5.0%) and a combination timing are unavailable in literature. The decrease in nal BCVA of sodium hyaluronate 3% and chondroitin sulfate 4% in an eye postoperatively as compared with the maximum achieved BCVA (2.5%). Interrupted sutures were applied in 14 cases (35.0%) was due to progression of corneal scarring and vascularisation for secure wound closure. All cases received subconjunctival 1% in most cases and secondary bacterial infection, diabetic papillo- dexamethasone 0.3 mL and gentamicin 0.3 mL (40 mg/mL) at pathy and in an eye each. The BCVA was mainly the conclusion of the surgery. Wherever surgery was prolonged spectacle-corrected visual acuity wherever PROSE was not or posterior capsular rent occurred, intracameral cefuroxime availed. (1 mg/0.1 mL) was administered. The intraoperative complications were encountered in six DISCUSSION cases and were managed in standard fashion (table 3). In the present communication, we report the largest series of patients with chronic sequelae of SJS who underwent cataract surgery. SJS is relatively rare and one of the most debilitating ocular surface diseases. We studied the visual outcomes and Table 3 Intraoperative complications during cataract surgery in challenges of cataract surgery in these patients and found Stevens–Johnson syndrome encouraging results. Type of No. of One of the major highlights of this study was the emergence Intraoperative complication surgery eyes Percentage of a characteristic pattern of visual recovery after cataract surgery in SJS (figure 2). There was a significant difference ’ Superior descemet s detachment Phaco 1 2.5 between the BCVA at presentation and the preoperative BCVA, Capsulorrhexis extension SICS 2 5.0 which may be attributed partly to increase in the density of the Superior ECCE 1 2.5 cataract during the course of the disease and to increasing Posterior capsular rent+vitreous ECCE 1 2.5 corneal haze. There was an evident increase in the BCVA in the prolapse immediate postoperative period. The visual acuity continued to Conversion of Phaco to ECCE Phaco 1 2.5 improve for a period of time after surgery to reach its maximum ECCE, extracapsular cataract extraction; Phaco, phacoemulsification; SICS, small in the median period of 1.5 months. However, the BCVA at the incision cataract surgery . last follow-up was almost similar to the immediate postoperative

1544 Narang P, et al. Br J Ophthalmol 2016;100:1542–1546. doi:10.1136/bjophthalmol-2015-308041 Downloaded from http://bjo.bmj.com/ on November 15, 2016 - Published by group.bmj.com Clinical science

Table 4 Comparison with a published literature (Iyer et al) in Stevens–Johnson syndrome No. of Postoperative Postoperative patients Type of cataract Improvement ocular corneal Study group (no. of eyes) surgery n (%) in BCVA (%) surface breakdown infection

Iyer et al 17 (22) Phaco 14 (63.6%) ECCE+IOL 6 (27.3%) 81.82 0 (0%) 0 (0%) ECCE 1 (4.5%) ICCE 1 (4.5%) Present study 32 (40) Phaco 26 (65%) ECCE+IOL 8 (20%) 97.5 4 (10%) 1 (2.5%) ECCE 1 (2.5%) SICS 5 (12.5%) BCVA, best-corrected visual acuity; ECCE, extracapsular cataract extraction; ICCE, intracapsular cataract extraction; IOL, intraocular lens; Phaco, phacoemulsification; SICS, small incision cataract surgery.

BCVA and lesser than the maximum achieved BCVA. This may postoperatively. These were managed successfully further proving be due to the progression of corneal scarring and vascularisation that adequately controlled ocular surface inflammation preopera- during the chronic course of this disease. tively and postoperatively were critical to a successful outcome. Limited information is available in literature on cataract Kasetsuwan et al9 cite the following factors to be implicated surgery in SJS. There are two case series and a case report on in exacerbation of ocular surface disease after cataract surgery: this topic so far.578A comparison of our study with a similar use of topical anaesthesia, transsection of the corneal nerves, study done by Iyer et al8 in which 22 eyes of 17 patients with exposure to intense illumination by the operating microscope, SJS underwent cataract surgery is shown in table 4. excessive irrigation of the tear film during surgery, elevation of ECCE, intracapsular cataract extraction and phacoemulsifica- inflammatory factors in the tear film due to ocular surface irrita- tion were included by Iyer et al.8 Sangwan and Burman5 tion postoperatively and topical medication with preservatives described three eyes which underwent ECCE only. However, after surgery. Topical non-steroidal anti-inflammatory drugs our series included ECCE, SICS and phacoemulsification. The (NSAIDs) such as nepafenac, ketorolac and diclofenac have been preferred type of cataract surgery in our series was phacoemulsi- reported to cause corneal melting mainly in the presence of epi- fication. The case report by Vasavada and Dholakia7 highlighted thelial breakdown.10 In our series too, NSAIDs were avoided. the use of controlled parameters in phacoemulsification of total Even though SJS is a rare disease, a significant sample size cataract in a patient with SJS. Appropriate technique and being could be achieved due to the extensive database of these patients within the confines of the capsulorrhexis were of paramount from this dedicated tertiary eye care centre. The weaknesses of importance. The authors emphasised the significance of the skill our study include its retrospective nature and lack of surgeon and experience of the surgeon while operating such cases. In and technique standardisation. However, to conduct a prospect- the presence of symblepharon and forniceal shortening, a tem- ive study on a rare condition like SJS is challenging. Another poral approach was favourable. The case series by Sangwan and weakness is the longer study duration. But, to get a significantly Burman reported that ECCE, either through a corneal or limbal large sample size, we had to cover all the cases during the past incision, could be done when central corneal clarity is compro- 11 years. The data hence gathered were a series of largest mised due to scarring.5 In the presence of severe peripheral number of such cases ever reported and can be an important corneal thinning, a limbal or scleral incision could be used. contribution to the existing sparse literature on this topic. Our Peribulbar blocks were preferred for most of the cases antici- study aimed at considering the visual outcomes of cataract pating a prolonged surgery due to compromised media clarity. surgery in SJS and postoperative was not considered The majority of the operated were posterior polar, pos- as corneal haze was significant in such cases. As this centre is terior subcapsular and early nuclear sclerosis. The patients in dedicated to comprehensive cornea care, the best visual correc- our series were different from routine cataract surgery patients. tion was provided, including the use of PROSE, wherever As any intervention in SJS carries a risk of surface breakdown possible. and related problems, we intervened when the cataract was sig- To summarise, our study describes a characteristic pattern of nificant enough to hamper day-to-day life of the patient. We visual recovery after cataract surgery in chronic sequelae of SJS, also believe it is important to operate on these cases in the early the importance of preoperative and postoperative ocular surface stages as soon as the ocular surface is stable. Waiting for the cat- integrity and the tips, techniques and outcomes of cataract aracts to become dense might lead to less favourable outcomes surgery in such cases. Keeping in view the visual needs of the as the corneal visibility will be progressively compromised. patient with SJS, an early cataract surgery can be undertaken The presentation of corneal condition in SJS is not uniform and after ocular surface stabilisation and treating the associated hence type of cataract surgery was decided based on this and the sequelae like dry and lid disorders appropriately (see intraoperative view available to the surgeon. Wherever appropri- online supplementary appendix 1). Appropriate cataract man- ate, capsular staining helped to identify the anterior capsule of the agement in these eyes can be visually rewarding for the patients lens during capsulorrhexis as well as during phacoemulsification of this rare but chronic and debilitating disorder. (to remain within the capsular bag). The careful placement of IOL in the capsular bag was desirable. The type of IOL (PMMA or Twitter Follow Ashik Mohamed at @mducityman acrylic) varied with the type of cataract surgery done. As the Contributors Design and conduct of the study: VSS; collection, management, ocular surface was the one affected and not the endothelium of analysis and interpretation of the data: PN, AM and VM; preparation of the fi the cornea, advantage of a particular irrigating solution or visco- manuscript: PN; review of the manuscript: AM, VM and VSS; nal approval of the manuscript: PN, AM, VM and VSS. elastic agent during cataract surgery was not evident. The compli- cations reported intraoperatively were common to any cataract Competing interests None declared. surgery with compromised media clarity. Though no postoperative Ethics approval Institutional Review Board, L V Prasad Eye Institute, Hyderabad, ocular surface breakdown and corneal infection was seen in the India. above study,8 we had four and one cases of each respectively, Provenance and peer review Not commissioned; externally peer reviewed.

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REFERENCES 5 Sangwan VS, Burman S. Cataract surgery in Stevens-Johnson syndrome. J Cataract 1 Holland EJ, Hardten DR. Stevens–Johnson syndrome. In: Pepose JS, Holland GN, Refract Surg 2005;31:860–2. Wilhelmus KR, eds. Ocular infection & immunity. St Louis, Missouri: Mosby, 6 Holladay JT. Visual acuity measurements. J Cataract Refract Surg 2004;30:287–90. 1996:416–25. 7 Vasavada AR, Dholakia SA. Phacoemulsification in total white cataract with 2 Kompella VB, Sangwan VS, Bansal AK, et al. Ophthalmic complications and Stevens-Johnson syndrome. Indian J Ophthalmol 2007;55:146–8. management of Stevens-Johnson syndrome at a tertiary eye care centre in south 8 Iyer G, Srinivasan B, Agarwal S, et al. Comprehensive approach to ocular India. Indian J Ophthalmol 2002;50:283–6. consequences of Stevens Johnson Syndrome—the aftermath of a systemic 3 Arstikaitis MJ. Ocular aftermath of Stevens-Johnson syndrome. Arch Ophthalmol condition. Graefes Arch Clin Exp Ophthalmol 2014;252:457–67. 1973;90:376–9. 9 Kasetsuwan N, Satitpitakul V, Changul T, et al. Incidence and pattern of dry eye 4 Di Pascuale MA, Espana EM, Liu DT, et al. Correlation of corneal complications with after cataract surgery. PLoS ONE 2013;8:e78657. cicatricial pathologies in patients with Stevens-Johnson syndrome and toxic 10 Wolf EJ, Kleiman LZ, Schrier A. Nepafenac-associated corneal melt. J Cataract epidermal necrolysis syndrome. 2005;112:904–12. Refract Surg 2007;33:1974–5.

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Cataract surgery in chronic Stevens− Johnson syndrome: aspects and outcomes

Purvasha Narang, Ashik Mohamed, Vikas Mittal and Virender S Sangwan

Br J Ophthalmol 2016 100: 1542-1546 originally published online February 22, 2016 doi: 10.1136/bjophthalmol-2015-308041

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