Publications by authors named "Swapna S Shanbhag"

42 Publications

Lid margin keratinization in Stevens-Johnson syndrome: Review of pathophysiology and histopathology.

Ocul Surf 2021 Apr 3. Epub 2021 Apr 3.

Centre for Ocular Regeneration (CORE), L V Prasad Eye Institute, Hyderabad, Telangana, India; Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India; The Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India. Electronic address:

Lid margin keratinization (LMK) is a chronic ocular sequela of Stevens-Johnson syndrome (SJS), which causes lid wiper epitheliopathy and progressive ocular surface damage. The exact etiopathogenesis of LMK, however, remains elusive. This review summarizes the potential pathophysiological mechanisms of LMK and describes its histopathological features. A literature search of articles discussing the pathophysiology of LMK in SJS was performed. The possible pathophysiologic mechanisms contributing to LMK, as identified on the literature review, included loss of the muco-cutaneous junction barrier leading to epidermalization, dyskeratosis involving the meibomian gland orifices, altered lid margin microbiome, and de novo squamous metaplasia of the marginal conjunctival epithelium. Based on these mechanisms, the possible sources of keratinized epithelium at the posterior lid margin in SJS could be the adjacent anterior eyelid skin, hyperkeratinized epithelium from the meibomian gland ductal orifices, or the inflamed marginal conjunctiva. The epithelial, sub-epithelial, and stromal changes seen in keratinized posterior lid margins in SJS patients undergoing mucous membrane grafting were also investigated. The findings revealed keratinizing squamous metaplasia of the posterior lid margin accompanied by subepithelial infiltration of helper T cells predominantly on the conjunctival side. The visible meibomian gland orifices had ductal hyperkeratinization and plugging. These findings support a role for inflammation in the pathogenesis of LMK in SJS. Future research can be directed at delineating the pathways that lead to LMK by studying the changes in the lid margin microbiome, and the molecular mechanisms regulating keratinization in the conjunctiva and the meibomian gland orifices in eyes affected by SJS.
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http://dx.doi.org/10.1016/j.jtos.2021.03.011DOI Listing
April 2021

Diphtheroids as Corneal Pathogens in Chronic Ocular Surface Disease in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Cornea 2021 Mar 8. Epub 2021 Mar 8.

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA; The Cornea Institute, L. V. Prasad Eye Institute, Hyderabad, India; and Infectious Disease Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.

Purpose: To characterize diphtheroid corneal infections in eyes in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

Methods: Observational case series.

Results: Four eyes of 3 patients were included in this review. Each eye presented with persistent corneal epithelial defect with corneal thinning in the chronic phase of SJS/TEN. None of the epithelial defects were associated with stromal infiltration. The corneas were cultured at the time of workup of persistent epithelial defect (3 eyes) or at time of tectonic penetrating keratoplasty after perforation (1 eye). Cultures yielded abundant growth of Corynebacterium spp., including Corynebacterium jeikeium (n = 2), Corynebacterium glucuronolyticum (n = 1), and a multidrug-resistant Corynebacterium striatum isolate (n = 1). The ocular surface was stabilized with surgical intervention (1 eye) or with introduction of fortified topical antibiotic based on laboratory identification and susceptibility testing of the isolated organisms (3 eyes). Numerous risk factors for microbial keratitis were present in all 4 eyes.

Conclusions: In eyes with a persistent corneal epithelial defect in the chronic phase of SJS/TEN, even in the absence of an infiltrate, corneal culture should be undertaken. Recognition and treatment of Corynebacterium spp. as opportunistic pathogens may lead to favorable outcomes in cases of clinically sterile ulceration during the chronic phase of SJS/TEN.
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http://dx.doi.org/10.1097/ICO.0000000000002696DOI Listing
March 2021

A beginner's guide to mucous membrane grafting for lid margin keratinization: Review of indications, surgical technique and clinical outcomes.

Indian J Ophthalmol 2021 04 28;69(4):794-805. Epub 2021 Jan 28.

The Cornea Institute; Center for Ocular Regeneration (CORE); Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, Telangana, India.

The posterior lid margin, where the mucocutaneous junction (MCJ) between the eyelid skin and tarsal conjunctiva is located, plays a critical role in maintaining the homeostasis of the ocular surface. Posterior migration of the MCJ leads to lid-margin keratinization (LMK), which has a domino effect on the delicate balance of the ocular surface microenvironment. This occurs most commonly following Stevens-Johnson syndrome/toxic epidermal necrolysis and is not known to regress spontaneously or with medical therapy. Over time, LMK causes blink-related chronic inflammatory damage to the corneal surface which may have blinding consequences. Lid-margin mucous membrane grafting (MMG) is the only definitive therapy for LMK. Timely MMG can significantly alter the natural course of the disease and not only preserve but even improve vision in affected eyes. Literature searches were conducted on PubMed, using the keywords "mucous membrane grafts," "lid margin keratinization," "Stevens-Johnson syndrome," "toxic epidermal necrolysis," "lid related keratopathy," and "lid wiper epitheliopathy". This review, which is a blend of evidence and experience, attempts to describe the indications, timing, surgical technique, postoperative regimen, and clinical outcomes of MMG for LMK. The review also covers the possible complications and pearls on how they can be effectively managed, including how suboptimal cosmetic outcomes can be avoided. The authors hope that this review will aid ophthalmologists, including cornea and oculoplasty specialists, to learn and perform this vision-saving surgery better, with the aim of helping their patients with chronic ocular surface disorders, relieving their suffering, and improving their quality of life.
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http://dx.doi.org/10.4103/ijo.IJO_1273_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012968PMC
April 2021

Tear secretion from the lacrimal gland: variations in normal versus dry eyes.

Br J Ophthalmol 2021 Feb 17. Epub 2021 Feb 17.

The Cornea Institute, LV Prasad Eye Institute, Hyderabad, Telangana, India

Purpose: To investigate the secretory status of the main lacrimal gland in healthy and dry eye disease (DED) via fluorescein-assisted direct assessment of tear secretion from the palpebral lobes.

Methods: Included were 25 healthy subjects (50 lobes) and 75 subjects with DED (cicatrising conjunctivitis (CC, n=27), evaporative dry eyes (EDE, n=25) and Sjogren's syndrome (SS, n=23)). Analysed parameters included number and location of ductular openings, tear flow rate per gland and per ductule, and the time lag for the initiation of secretion.

Results: Ductular openings could be observed in all patients with EDE and healthy subjects whereas only 33% (18/54) glands of CC patients and 67% glands (31/46) patients with SS revealed ductules. The median number of ductules per lobe was 4 in normal (range 3-5), 3 in EDE (3-6), 1 in SS (0-3) and 0 in CC group (0-3) (p<0.000001). The median tear flow rate per lobe in CC (0.00 [Formula: see text]) and SS (0.21 [Formula: see text]) was significantly lesser than normal lobes (1.05 [Formula: see text], and EDE (0.99 [Formula: see text] eyes. The tear flow rate differed significantly between SS and CC group (p<0.0001). The maximum time lag occurred in the CC group (median, 20 s), followed by the SS group (median, 1.5 s) whereas the EDE group had similar time lag (<1 s) as of normal glands (p<0.0001).

Conclusion: Direct assessment of tear secretion from the palpebral lobe demonstrates significant differences between EDE, aqueous deficient dry eye and dry eye in CC.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318159DOI Listing
February 2021

Genetic Markers for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in the Asian Indian Population: Implications on Prevention.

Front Genet 2020 12;11:607532. Epub 2021 Jan 12.

The Cornea Institute, L.V. Prasad Eye Institute, Hyderabad, India.

This review attempts to collate all the studies performed in India or comprising a population originating from India and to find out if there is an association between the HLA (human leucocyte antigen) type of individual and development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) subsequent to medication use. The authors performed a PubMed search of all articles published in English from 2009 to 2019 for articles that studied HLA type in patients who developed SJS/TEN after intake of a specific drug in the Asian Indian population or in individuals of Asian Indian origin. The selection criteria were satisfied by a total of 11 studies that reported HLA associations with specific drugs, which induced SJS/TEN, mainly anti-epileptic drugs, and cold medicine/non-steroidal anti-inflammatory drugs. These studies involved a small number of patients, and hence, there is limited evidence to conclude if these associations can be extrapolated to a larger population of the same ethnicity. Similar multi-center studies need to be conducted with a larger sample size to confirm these associations. This would have implications in policy making and for understanding the potential of using genetic markers as a screening tool before prescribing a drug to a patient, which might make them susceptible to developing a potentially life-threatening disease such as SJS/TEN. This is possibly the only mode of primary prevention for this potentially fatal severe cutaneous adverse drug reaction.
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http://dx.doi.org/10.3389/fgene.2020.607532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837290PMC
January 2021

An Evidence-Based Strategic Approach to Prevention and Treatment of Dry Eye Disease, a Modern Global Epidemic.

Healthcare (Basel) 2021 Jan 17;9(1). Epub 2021 Jan 17.

The Cornea Institute, L V Prasad Eye Institute, Hyderabad 500034, India.

Dry eye disease (DED) is an emerging health concern causing significant visual, psychological, social, and economic impact globally. In contrast to visual rehabilitation undertaken at late stages of DED, measures instituted to prevent its onset, establishment, or progression can alter its natural course and effectively bring down the associated morbidity. This review attempts to present the available literature on preventive strategies of DED at one place, including strategies for risk assessment and mitigation, targeting a wide range of population. A literature search was conducted using PubMed and an extensive literature review on preventive strategies for DED was compiled to put forth a holistic and strategic approach for preventing DED. This can be undertaken at various stages or severity of DED directed at different tiers of the health care system. Conclusion: This review intends to put emphasis on preventive strategies being adopted as an integral part of routine clinical practice by general ophthalmologists and specialists to tackle the burden of DED and improve the quality of the lives of the patients suffering from it.
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http://dx.doi.org/10.3390/healthcare9010089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830429PMC
January 2021

Commentary: The role of amniotic membrane transplantation in the management of acute ocular chemical burns.

Indian J Ophthalmol 2021 01;69(1):64-65

The Cornea Institute; Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India.

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http://dx.doi.org/10.4103/ijo.IJO_2040_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926167PMC
January 2021

Serial anterior segment optical coherence tomography post autologous simple limbal epithelial transplantation.

BMJ Case Rep 2020 Dec 13;13(12). Epub 2020 Dec 13.

The Cornea Institute, LV Prasad Eye Institute, Hyderabad, Telangana, India

A 24-year-old young man presented to us with total limbal stem cell deficiency (LSCD) in the right eye 1 year post ocular chemical burn. The patient subsequently underwent limbal biopsy in the healthy contralateral eye and autologous simple limbal epithelial transplantation in the right eye. The patient was followed up with sequential imaging of the cornea with high-resolution anterior segment optical coherence tomography (HR-ASOCT) for 3 years. The serial HR-ASOCT imaging in the operated eye showed regeneration of the epithelium from the limbal transplant over the human amniotic membrane (hAM) with integration of the transplant within the cornea with subepithelial retention of the hAM. Over the long-term follow-up, thinning of the hAM and thickening of the epithelium was noted. At 3 years, the cornea maintained an intact epithelium with no signs of recurrence of LSCD.
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http://dx.doi.org/10.1136/bcr-2020-236692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737076PMC
December 2020

Simultaneous surgical management of unilateral limbal stem cell deficiency and symblepharon post chemical burn.

BMJ Case Rep 2020 Dec 9;13(12). Epub 2020 Dec 9.

The Cornea Institute, LV Prasad Eye Institute, Hyderabad, Telangana, India

A 6-year-old female child presented with severe acute ocular chemical burn in the right eye 2 days after injury with cement. She underwent removal of all foreign bodies from the ocular surface and amniotic membrane transplantation. Three months later, she developed unilateral total limbal stem cell deficiency (LSCD) with symblepharon in two quadrants. Three months after the acute injury, the patient underwent autologous simple limbal epithelial transplant in the right eye with one-clock hour of limbus harvested from the left eye. At the same sitting, she underwent symblepharon release in two quadrants of the right eye with conjunctival autograft harvested from the left eye followed by conjunctival graft suturing to the areas of bare sclera in the right eye. One year after surgery, the patient's visual acuity improved from counting fingers close to face preoperatively to 20/50 (uncorrected) with no recurrence of LSCD or symblepharon.
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http://dx.doi.org/10.1136/bcr-2020-237234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733107PMC
December 2020

Oral mucous membrane grafts for total symblepharon and lid margin keratinisation post Stevens-Johnson syndrome.

BMJ Case Rep 2020 Oct 31;13(10). Epub 2020 Oct 31.

The Cornea Institute, LV Prasad Eye Institute, Hyderabad, India

A female patient in her late 40s presented with severe visual impairment and a history of oral ulcers, necrolysis of skin and hospitalisation after using gabapentin for neck pain 10 months ago. She was a diagnosed case of Stevens-Johnson syndrome (SJS) with chronic ocular sequelae-with total symblepharon and keratinised lid margins in the left eye and limbal stem cell deficiency and severe dryness in the right eye. Her visual acuity was perception of light in both eyes. She underwent left eye symblepharon release with autologous labial mucous membrane grafts (MMGs) for surface reconstruction and subsequent lid margin MMG for lid margin keratinisation. Best-corrected visual acuity improved to 20/25 with scleral lens in the left eye, which was sustained over 1 year of follow-up. Labial mucosa acts as a useful and easily accessible alternative to conjunctiva in eyes with bilateral severe ocular surface damage and total symblepharon secondary to SJS.
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http://dx.doi.org/10.1136/bcr-2020-239383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783625PMC
October 2020

Chronic cicatrizing conjunctivitis: A review of the differential diagnosis and an algorithmic approach to management.

Indian J Ophthalmol 2020 Nov;68(11):2349-2355

The Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India.

Cicatrizing conjunctivitis constitutes a group of chronic local and systemic disorders that cause conjunctival scarring. A systematic approach is required to sift through the clinical history, examination, and laboratory investigations of patients to arrive at the correct diagnosis of the underlying cause. Establishing the etiology is critical, as the therapeutic approach changes based on the cause of conjunctival inflammation. Effective management of patients with the condition requires knowledge of multiple modalities such as systemic immunosuppressive therapy, use of scleral contact lenses, and surgery for ocular surface and vision improvement. We review the clinical features of this condition and present diagnostic and treatment algorithms to help simplify the complexities in its management. This review attempts to place all the relevant information on chronic cicatrizing conjunctivitis together in one place for the benefit of cornea and ocular surface specialists, general ophthalmologists, and ophthalmology residents.
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http://dx.doi.org/10.4103/ijo.IJO_604_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774214PMC
November 2020

Cataract Surgery in Dry Eye Disease: Visual Outcomes and Complications.

Front Med (Lausanne) 2020 7;7:575834. Epub 2020 Oct 7.

The Cornea Institute, L V Prasad Eye Institute, Hyderabad, India.

To describe the visual outcomes and complications following cataract surgery in dry eye disease (DED). This retrospective study included 668 eyes of 399 patients with DED, who underwent cataract surgery between 2011 and 2019 at our multi-tier ophthalmology hospital network. Based on etiology, they were divided into three groups: cicatrizing conjunctivitis (CC), meibomian gland dysfunction (MGD), and Sjogren's syndrome (SS). The data on demographics, visual impairment, surgical technique, visual outcomes, and complications were collected using an electronic medical record system. Median LogMAR best corrected visual acuity (BCVA) with interquartile range (IQR) was compared using Wilcoxon's rank sum test. The median age at which cataract surgery was performed was 58 (IQR: 47-65) years. Etiology of DED was CC in 279, MGD in 255, and SS in 134 eyes. Most (471) eyes underwent phacoemulsification, under peribulbar anesthesia (548) through a temporal clear corneal incision (209) with foldable intraocular lens implantation (417). The overall median LogMAR BCVA improved from 1.1 (IQR: 0.6-2.1) at baseline to 0.3 (IQR: 0.1-0.7) and 0.1 (IQR: 0-0.65) at 1 and 6 weeks ( < 0.0001) post-operatively. The median 6 weeks post-operative BCVA was 0.3, 0.1, and 0.1 in CC, MGD, and SS, respectively, and significantly better than at baseline ( < 0.0001). The leading cause of sub-optimal vision was corneal scarring (44; 9%), and the most common complication was posterior capsular rupture with vitreous loss (23; 3%). Cataract surgery has good visual outcomes in patients with DED, without any disconcerting rate of complications. Pre-existing keratopathy is the main determinant of the extent of post-operative visual recovery.
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http://dx.doi.org/10.3389/fmed.2020.575834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575780PMC
October 2020

Palpebral lobe of the human lacrimal gland: morphometric analysis in normal versus dry eyes.

Br J Ophthalmol 2020 Sep 12. Epub 2020 Sep 12.

Centre for Ocular Regeneration, LV Prasad Eye Institute, Hyderabad, Telangana, India

Aim: To study the morphological features of the palpebral lobe of the main lacrimal gland in normal and dry eyes.

Methods: This cross-sectional study included 25 healthy subjects and 83 patients with dry eye disease (DED). The aetiological groups of DED were cicatrising conjunctivitis (CC, n=35), evaporative dry eyes (EDE, n=25) and Sjogren's syndrome (SS, n=23). The palpebral lobes in both eyes were evaluated using slit-lamp biomicroscopy and photography for size (exposed area in mm), shape (convex or flat), presence of cicatrisation (scarring and/or symblepharon) and appearance of the overlying conjunctival vessels.

Results: The palpebral lobes in the normal and EDE group were similar in terms of size (41.5±15.6 mm vs 39±12.2 mm, p=0.203), convex shape (100%) and absence of cicatrisation or vascular engorgement (0%). However, as compared to normal controls, the size of the palpebral lobe was markedly reduced in the SS (27.9±12.3, p<0.0001) and CC (18.1±13.7, p<0.0001) groups. The size of the lobes was asymmetric in the CC group (p<0.0001) and differed significantly from the SS group (p=0.0003). Flat contour (79% vs 50%, p=0.0028), subepithelial scarring with or without symblepharon (52% vs 13%, p<0.0001) and engorged conjunctival vessels (96% vs 63%, p=0.00011) were seen in a significantly higher proportion of lobes in the CC as compared to the SS group.

Conclusion: The morphological features of the palpebral lobe of the main lacrimal gland are significantly distorted in aqueous deficient dry eyes due to CC and SS; however, the lobes in patients with EDE are similar to normal eyes.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316929DOI Listing
September 2020

Lid-Related Keratopathy in Stevens-Johnson Syndrome: Natural Course and Impact of Therapeutic Interventions in Children and Adults.

Am J Ophthalmol 2020 11 15;219:357-365. Epub 2020 Jul 15.

The Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India; Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India. Electronic address:

Purpose: To compare the long-term visual outcomes of different management strategies in children and adults with Stevens-Johnson Syndrome (SJS)-induced chronic lid-related keratopathy.

Design: Retrospective comparative case series.

Methods: This study included 705 eyes of 401 patients (81 children and 320 adults) with SJS who presented with chronic lid-related keratopathy between 1990 and 2015. Affected eyes received either conservative therapy [topical medications (n = 363)] or definitive management (n = 342) that included mucous membrane grafting (MMG), prosthetic replacement of the ocular surface ecosystem (PROSE) contact lenses, or both. The primary outcome measure was change in best corrected visual acuity (BCVA) over time. The secondary outcome measure was the odds of developing corneal ulceration or perforation in the first year.

Results: The treatment subgroups were comparable at baseline in terms of BCVA and previous management (P > .10). Over 10 years, children and adults who received conservative therapy lost at least 5 lines of median BCVA and carried a 3 times higher risk of developing corneal ulceration in the first year. Conversely, definitive therapy provided significant benefit by improving median BCVA (P < .0001). In children, MMG was more effective than PROSE (P = .009), whereas PROSE was more effective than MMG in adults (P = .028). However, the combination of MMG followed by PROSE provided the best results in both children and adults (P < .036).

Conclusions: Both MMG and PROSE changed the natural course and helped in preserving and improving vision in eyes with SJS-induced lid-related keratopathy. Regardless of age, those who received both MMG and PROSE had the best long-term visual outcomes.
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http://dx.doi.org/10.1016/j.ajo.2020.07.006DOI Listing
November 2020

Outcomes of the Boston type 1 and the Aurolab keratoprosthesis in eyes with limbal stem cell deficiency.

Br J Ophthalmol 2021 Apr 17;105(4):473-478. Epub 2020 Jun 17.

The Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India

Purpose: To analyse the outcomes of keratoprosthesis in eyes with limbal stem cell deficiency (LSCD) and to compare the outcomes in two different keratoprosthesis devices.

Methods: This was a single-centre retrospective comparative case series which included 81 eyes of patients with severe bilateral corneal blindness secondary to LSCD. The patients underwent either Boston type 1 keratoprosthesis (Boston Kpro, n=44) or Aurolab keratoprosthesis (AuroKpro, n=37) implantation. The primary outcome measures of anatomical retention and functional recovery of 20/200 or better visual acuity at yearly time points until 5 years of follow-up were compared between the two groups.

Results: The most common indication overall was chemical injury (64.2%). Anatomical retention rates were similar in the Boston Kpro (30/44, 68.2%) and AuroKpro (23/37, 62.2%) groups (p=0.89). Kaplan-Meier survival rates at 5 years of follow-up were greater for the Boston Kpro group with respect to both anatomical retention (58.51%±9% vs 43.8±12%; p=0.23) as well as functional recovery (42.61%±8% vs 35.03±10%; p=0.9); these differences were not statistically significant. Overall, the most common complication was new-onset glaucoma (59%; 48/81). The difference in incidence rate of this complication was not statistically significant among the two groups (p=0.09).

Conclusion: Keratoprosthesis is an effective treatment option for patients with corneal blindness secondary to LSCD. In a setting where LSCD is a common cause of corneal blindness, the AuroKpro, when available can be considered an alternative to the Boston Kpro to achieve anatomical and functional success in patients who otherwise would not have access to this device.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316369DOI Listing
April 2021

Multidisciplinary care in Stevens-Johnson syndrome.

Ther Adv Chronic Dis 2020 28;11:2040622319894469. Epub 2020 Apr 28.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114, USA.

Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are potentially fatal mucocutaneous diseases that can involve many organ systems. Manifestations of SJS/TEN outside of the skin, eyes, and oral mucosa are not well defined or well recognized, and, therefore, are often not addressed clinically. As supportive care improves and mortality from SJS/TEN decreases, chronic complications in affected organ systems are becoming more prevalent. Recognition of the manifestations of SJS/TEN in the acute phase is critical to optimal care. In this review, we review the organ systems that may be involved in SJS/TEN, provide an overview of their management, and propose a list of items that should be communicated to the patient and family upon discharge. The organ systems discussed include the pulmonary, gastrointestinal/hepatic, oral, otorhinolaryngologic, gynecologic, genitourinary, and renal systems. In addition, the significant psychosocial, nutritional, and pain consequences and management of SJS/TEN are discussed.
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http://dx.doi.org/10.1177/2040622319894469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236394PMC
April 2020

The effects of systemic cyclosporine in acute Stevens-Johnson syndrome/toxic epidermal necrolysis on ocular disease.

Ocul Surf 2021 01 20;19:128-132. Epub 2020 May 20.

Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:

Purpose: To evaluate the effect of systemic cyclosporine (CsA) on ocular disease in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients.

Methods: In this retrospective, comparative cohort study at a single center, patients with a diagnosis of SJS/TEN and with at least 3 months of follow up were divided into two groups: those who received systemic CsA and those who did not receive systemic CsA. Best-corrected visual acuity (BCVA) and chronic ocular surface complications score (COCS) at final follow-up were compared between the two groups.

Results: The median age and follow-up period of patients was 29 years (range, 1.5-71 years) and 16.8 months (range, 3.67-91.58 months), respectively. BCVA, COCS, meibomian gland dysfunction, limbal stem cell deficiency, and the need for mucous membrane grafting and scleral lenses were not significantly different between patients who received systemic CsA as compared to patients who did not receive systemic CsA.

Conclusions: In this small cohort of patients with SJS/TEN, we could identify no association between the use of systemic CsA as a component of their initial therapy and chronic ocular complications.
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http://dx.doi.org/10.1016/j.jtos.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811361PMC
January 2021

Long-term outcomes of amniotic membrane treatment in acute Stevens-Johnson syndrome/toxic epidermal necrolysis.

Ocul Surf 2020 07 19;18(3):517-522. Epub 2020 Mar 19.

Department of Ophthalmology, Massachusetts Eye & Ear, Boston, MA, USA. Electronic address:

Purpose: To report the long-term outcomes of amniotic membrane (AM) use in the form of transplantation (AMT) and self-retained amniotic membrane (ProKera® device, PD) in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

Methods: Electronic records of all patients with a diagnosis of SJS/TEN at Massachusetts Eye and Ear between January 2008 and January 2018 were reviewed. Patients who received AM in acute SJS/TEN were selected. Only patients with follow-up ≥ 3 months after discharge were included.

Results: Data of 55 eyes of 29 patients were analyzed. All 55 eyes received the first AM at a median interval of 5 days (inter-quartile range (IQR): 3-7 days) after onset of skin rash. Fifty-six percent of eyes (31/55) received AMT while 44% (24/55) received PD. Forty percent of eyes (22/55) required a repeat AMT or PD. Median follow-up after initial AM was 2.5 years (IQR: 1.2-3.6 years). At last follow-up, the best-corrected visual acuity was ≥20/40 in 87% of eyes (48/55). The most common complications in the chronic phase were meibomian gland disease and dry eye, seen in 78% of eyes (43/55) and 58% of eyes (32/55) respectively.

Conclusions: Long-term results show that early use of AM in the acute phase of SJS/TEN may be effective in mitigating severe vision loss after SJS/TEN. However, eyelid-related complications and dry eye remain a common problem even with the use of AM.
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http://dx.doi.org/10.1016/j.jtos.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811362PMC
July 2020

Multidisciplinary Treatment to Restore Vision in Ocular Burns.

J Burn Care Res 2020 07;41(4):859-865

Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston.

Periorbital burns generate contraction and distortion of periorbital soft tissue, causing eyelid malfunction, further contributing to loss of vision from corneal scarring or perforation. We present our multidisciplinary algorithm to restore vision in patients with burn-related bilateral corneal blindness with light perception. Chart review was performed for four consecutive burn patients requiring periocular reconstruction and keratoprosthesis. Initial treatment included globe coverage with eyelid releases and grafts. Strategy of corneal replacement was determined by eyelid position and function and sufficiency of tear production. All patients were corneal blind with light perception only and cicatricial ectropion. The eye with better visual prognosis was reconstructed. Eyelid reconstruction procedures consisted of lid releases with full-thickness skin graft (FTSG) or split-thickness skin graft (STSG). Two patients regained adequate lid function and underwent standard keratoprosthesis placement. Two underwent mucous membrane grafts followed by keratoprosthesis. All patients experienced improved postoperative vision in their reconstructed eye. Corneal injury due to periocular burns can lead to blindness. Early involvement of ophthalmology, protective measures, and early ectropion release are critical. For severe burns, a multidisciplinary approach, where adequate globe protection is followed by keratoprosthesis placement, can effectively restore vision in patients with burn-related corneal blindness.
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http://dx.doi.org/10.1093/jbcr/irz201DOI Listing
July 2020

Clinical clues predictive of Stevens-Johnson syndrome as the cause of chronic cicatrising conjunctivitis.

Br J Ophthalmol 2020 07 19;104(7):1005-1009. Epub 2019 Oct 19.

Tej Kohli Cornea Institute, LV Prasad Eye Institute, Hyderabad, India

Purpose: This study aimed to identify the clinical clues in patients with chronic cicatrising conjunctivitis (CCC), that were suggestive of Stevens-Johnson syndrome (SJS) as the aetiology.

Methods: This was a cross-sectional observational study of 75 patients presenting with CCC from 2016 to 2018. Those with a documented diagnosis of SJS (n=43) were included as cases; while those with a positive serology or tissue biopsy for a non-SJS condition were included as controls (n=32). The features in the medical history and clinical examination that were positively and negatively associated with SJS were scored +1 and -1, respectively. A receiver operating characteristic (ROC) curve analysis was performed to detect the threshold score for optimal sensitivity and specificity of the scoring system.

Results: No single feature had absolute sensitivity and specify for SJS. The 10 positive features suggestive of SJS (p<0.0001) included (1) history of: acute conjunctivitis, fever or drug intake preceding conjunctivitis, peeling of skin on pressure, loss of nails and severe morbidity with hospital admission; and (2) clinical features of: skin discoloration, nail disfigurement, lip-margin dermalisation, lid-margin keratinisation and distichiasis. The two negative criteria were history of mucosal ulcers without skin involvement and recurrent mucosal ulceration. On ROC analysis, a score of >5 showed a sensitivity of 90.7% and specificity of 93.8% for the diagnosis of SJS.

Conclusions: The combination of clinical clues identified in this study can help clinicians confirm SJS as the aetiology of conjunctival cicatrisation, especially when reliable documentation of the acute episode is not available.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314928DOI Listing
July 2020

Authors' response to: The Perils and Pitfalls of Big Data analysis in medicine.

Ocul Surf 2019 10 22;17(4):840-841. Epub 2019 Aug 22.

Tej Kohli Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India; Center for Ocular Regeneration (CORE), L V Prasad Eye Institute, Hyderabad, Telangana, India. Electronic address:

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http://dx.doi.org/10.1016/j.jtos.2019.08.009DOI Listing
October 2019

Simple limbal epithelial transplantation (SLET): Review of indications, surgical technique, mechanism, outcomes, limitations, and impact.

Indian J Ophthalmol 2019 08;67(8):1265-1277

Tej Kohli Cornea Institute; Center for Ocular Regeneration (CORE), L V Prasad Eye Institute, Hyderabad, Telangana, India.

Simple limbal epithelial transplantation (SLET) is an innovative limbal stem cell transplantation technique that has gained increasing popularity over the last few years. Different groups from across the world have published the clinical results of SLET in large case series with varying types and severities of limbal stem cell deficiency (LSCD). This review attempts to place all the available knowledge on SLET together in one place for the benefit of not only cornea specialists and trainees but also for residents and general ophthalmologists. It follows a balanced approach of blending evidence with experience by providing an objective analysis of published results along with helpful insights from subject experts, starting from preoperative considerations including the role of newer imaging modalities to the technical aspects of the surgery itself and the management of possible complications. Original data and novel insights on allogeneic SLET for bilateral LSCD are included in the review to address the few remaining lacunae in the existing literature on this topic. This review intends to inform, educate, and empower all aspiring and practicing SLET surgeons to optimize their clinical outcomes and to have maximal positive impact on the lives of the individuals affected by unilateral or bilateral chronic LSCD.
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http://dx.doi.org/10.4103/ijo.IJO_117_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677059PMC
August 2019

Long-Term Effect of a Treatment Protocol for Acute Ocular Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Am J Ophthalmol 2019 12 19;208:331-341. Epub 2019 Jul 19.

Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA. Electronic address:

Purpose: To describe the long-term effect of a treatment protocol for ocular involvement in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), including focused ocular examination and pathology-appropriate use of lubrication, topical corticosteroids, topical antibiotics, and amniotic membrane transplantation (AMT).

Design: Retrospective, comparative case series.

Methods: A total of 48 patients (96 eyes) were included in this study. Nine of 48 patients (18 eyes) had acute SJS/TEN from 2000 to 2007 and did not receive protocol care (Group I). Thirty-nine of 48 patients (78 eyes) had acute SJS/TEN from 2008 to 2017 and received protocol care (Group II). The main outcome measures were best-corrected visual acuity (BCVA) at final follow-up visit and incidence of complications in the chronic phase.

Results: No eyes in Group I received AMT for SJS/TEN, compared to 87% of qualifying eyes in Group II (P < .0001) There was a significant difference in the proportion of eyes with BCVA ≥20/40 at last follow-up between Group I and Group II (33% vs 92%, P < .001). The proportion of eyes with vision-threatening complications in the chronic phase was significantly higher in Group I versus Group II (67% vs 17%, P = .002), with most complications occurring in the first 2 years after disease onset in both groups.

Conclusions: A specific protocol for acute ocular care in SJS/TEN, including aggressive use of AMT, was highly successful in reducing corneal blindness and severe vision-threatening complications of the disorder.
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http://dx.doi.org/10.1016/j.ajo.2019.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935472PMC
December 2019

Authors' response: Povidone-Iodine for the Treatment of Microbial Keratitis.

Surv Ophthalmol 2019 Nov - Dec;64(6):892-893. Epub 2019 Jul 5.

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA; Infectious Disease Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

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http://dx.doi.org/10.1016/j.survophthal.2019.06.005DOI Listing
January 2020

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration.

Curr Eye Res 2020 03 19;45(3):265-277. Epub 2019 Jul 19.

Center for Ocular Regeneration (CORE), L V Prasad Eye Institute, Hyderabad, India.

Corneal pathologies are a major cause of blindness and visual impairment, especially in the developing world. However, not only is there a global shortage of donor corneal tissue, but a significant proportion of these blinding pathologies also carry an unfavourable long-term prognosis for conventional corneal transplantation. In the last few decades, there has been a spurt of research on developing alternate approaches to address corneal blindness, including stem cell therapy. After the discovery of epithelial stem cells at the limbus, successful cell-based approaches to treat severe ocular surface disease were developed and have subsequently become widely practised across the world. More recently, mesenchymal stem cells were identified near the epithelial stem cells at the limbus, providing a unique opportunity to develop regenerative therapies for both corneal epithelial and stromal pathologies. This review firstly emphasises on qualifying limbal stem cells as either epithelial or mesenchymal and then summarises all the existing knowledge on both cell types and their individual roles in corneal regeneration.  The review describes the history, indications, techniques, and outcomes of the different methods of limbal epithelial stem cell transplantation and elaborates on the potential applications of limbal mesenchymal stem cell therapy.
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http://dx.doi.org/10.1080/02713683.2019.1639765DOI Listing
March 2020

Glaucoma Management in Patients With Aniridia and Boston Type 1 Keratoprosthesis.

Am J Ophthalmol 2019 11 24;207:258-267. Epub 2019 Jun 24.

Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil.

Purpose: To assess outcomes and glaucoma management in eyes with aniridia following Boston type 1 Keratoprosthesis (KPro) implantation.

Design: Retrospective, interventional comparative case series.

Methods: The population included patients with aniridia and patients with other preoperative diagnoses (excluding Stevens-Johnson syndrome, mucous membrane pemphigoid, and congenital disorders) who underwent KPro implantation at Massachusetts Eye and Ear with at least 2 years of follow-up. One eye per patient was selected based on the longer follow-up time. The main outcome was intermediate and long-term outcomes related to glaucoma.

Results: The aniridia (n = 22) and comparison (n = 61) groups had similar preoperative visual acuity (VA, mean ± standard deviation, 1.86 ± 0.52 logMAR, P = .33) and follow-up time (65.6 ± 26.3 months, P = .25). Before KPro implantation, eyes with aniridia had more glaucoma (76.2%) and glaucoma surgery (57.1%) than comparison eyes (51.8%, P = .053; 23.2%, P = .005, respectively). More Ahmed valves were co-implanted with KPro in aniridia (47.6%) vs comparison eyes (17.9%, P = .008). At final follow-up, more aniridia eyes had glaucoma (90.5%) than comparison eyes (64.3%, P = .02), but the 2 groups had similar percentages of eyes with cup-to-disc ratio (CDR) >0.8 (23.8% vs. 30.4%, P = .57) or CDR progression of ≥0.2 (42.9% vs 44.6%, P = .89, respectively). None of the eyes with prophylactic tube implantation developed glaucoma. Eyes with and without aniridia did not differ in post-KPro VA improvement (72.7%, 72.1%, P = .96), and final VA (1.28 ± 0.79 logMAR, 1.23 ± 0.98 logMAR, P = .51).

Conclusion: Despite a higher glaucoma prevalence, eyes with aniridia achieved similar VA as comparison eyes with more than 5 years of mean follow-up time. Boston KPro offers satisfactory visual rehabilitation in aniridia when glaucoma is managed aggressively.
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http://dx.doi.org/10.1016/j.ajo.2019.06.018DOI Listing
November 2019

Autologous limbal stem cell transplantation: a systematic review of clinical outcomes with different surgical techniques.

Br J Ophthalmol 2020 02 22;104(2):247-253. Epub 2019 May 22.

Center for Ocular Regeneration (CORE), LV Prasad Eye Institute, Hyderabad, India

Purpose: To conduct a systematic review on outcomes of three different techniques of autologous limbal stem cell transplantation (LSCT): conjunctival-limbal autografting (CLAu), cultivated limbal epithelial transplantation (CLET) and simple limbal epithelial transplantation (SLET), in unilateral limbal stem cell deficiency (LSCD).

Methods: Literature searches were conducted in MEDLINE (Ovid), Embase, Web of Science and Cochrane Central Register. Standard systematic review methodology was followed using Meta-analysis of Observational Studies in Epidemiology guidelines. Studies with a sample size of more than 10 eyes were included. The primary outcome measure of efficacy was restoration of a completely epithelised, stable and avascular corneal surface (anatomical success). The secondary outcome measure of efficacy was improvement in best-corrected visual acuity of two-lines or greater (functional success).

Results: The review identified 22 non-comparative case series, which included 1023 eyes. Ocular burns were the major (88%) indication for surgery. Overall, at a median postoperative follow-up of 1.75 years, autologous LSCT for unilateral LSCD showed anatomical and functional success rates of 69% and 60%, respectively, without any serious adverse events in the donor eye. The follow-up duration and indications for surgery were comparable across all groups (p>0.05). The anatomical and functional success rates of SLET (78%; 68.6%) and CLAu (81%; 74.4%) were comparable, and significantly better than those of CLET (61.4%; 53%; p=0.0048).

Conclusion: Autologous LSCT is a safe and effective treatment for unilateral LSCD. In the absence of randomised controlled trials, existing evidence clearly suggests that clinical outcomes are better with SLET and CLAu as compared with CLET.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314081DOI Listing
February 2020

Controversial role of retinoids in ocular surface disease.

Br J Ophthalmol 2019 08 25;103(8):1013-1014. Epub 2019 Apr 25.

Tej Kohli Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India

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http://dx.doi.org/10.1136/bjophthalmol-2019-314241DOI Listing
August 2019

Commentary: The human amniotic membrane: Fortifying nature's gift to ophthalmology.

Indian J Ophthalmol 2019 04;67(4):476

Tej Kohli Cornea Institute; Center for Ocular Regeneration (CORE), L V Prasad Eye Institute, Hyderabad, Telangana, India.

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http://dx.doi.org/10.4103/ijo.IJO_2062_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446629PMC
April 2019