Shweta Agarwal

Lacrimal Proline Rich 4 (LPRR4) Protein in the Tear Fluid Is a Potential Biomarker of Dry Eye Syndrome

Dry eye syndrome (DES) is a complex, multifactorial, immune-associated disorder of the tear and ocular surface. DES with a high prevalence world over needs identification of potential biomarkers so as to understand not only the disease mechanism but also to identify drug targets. In this study we looked for differentially expressed proteins in tear samples of DES to arrive at characteristic biomarkers. As part of a prospective case-control study, tear specimen were collected using Schirmer strips from 129 dry eye cases and 73 age matched controls. 2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. One of the differentially expressed protein in DES is lacrimal proline rich 4 protein (LPRR4). LPRR4 protein expression was quantified by enzyme immune sorbent assay (ELISA). LPRR4 was down regulated significantly in all types of dry eye cases, correlating with the disease severity as measured by clinical investigations. Further characterization of the protein is required to assess its therapeutic potential in DES.

Laminar Resorption in Modified Osteo-odonto-keratoprosthesis Procedure: A Cause for Concern

PURPOSE To analyze the cases of lamina resorption following the modified osteo-odonto-keratoprosthesis (MOOKP) procedure. DESIGN Retrospective case series. PATIENTS AND METHODS Case records of 18 eyes (20 laminae) of 17 patients who showed evidence of lamina resorption out of the 85 eyes (87 laminae) of 82 patients that underwent MOOKP procedure between March 2003 and March 2013 were analyzed. RESULTS Of the 17 patients (20 laminae), 1 underwent MOOKP procedure following multiple graft failures, 6 (7 laminae) belonged to the chemical injury group, and 10 (12 laminae) to the Stevens-Johnson syndrome (SJS) group. Resorption was noted in 20 out of 87 laminae (22.98%). The need for removal of lamina/extrusion was noted in 3 out of the 7 laminae in the chemical injury group and 8 out of the 12 laminae in the SJS group. The mean duration to the first sign suggestive of resorption among patients of SJS was 36.7 months and among patients of chemical injury was 43 months. Vitritis was the presenting feature (7 of 20 laminae, 35%) indicative of early resorption, and the occurrence of the same in eyes with lamina resorption was noted to be statistically significant in comparison to controls (P<.001). Sixteen out of 20 laminae showed evidence of resorption superiorly. CONCLUSION Vitritis was the most common presenting feature of lamina resorption and could be an indicator of lamina resorption. Resorption of the laminae was noted to occur along the aspect with thinner bone support in all eyes. Incidence of severe resorption with extrusion of cylinder/requiring lamina removal was noted to be higher among patients with SJS.

Treatment Modalities and Clinical Outcomes in Ocular Sequelae of Stevens-Johnson Syndrome Over 25 Years--A Paradigm Shift.

Purpose: To highlight and compare the outcomes of management for the ocular sequelae of Stevens–Johnson syndrome (SJS) over 25 years in a tertiary eye care institute. Methods: A retrospective chart review of 798 eyes of 399 patients with SJS evaluated between January 1990 and December 2004 (group I) and of 847 eyes of 517 patients between January 2005 and December 2014 (group II) was done. The primary and secondary outcome measures were a change in the best-corrected visual acuity (BCVA) and an improvement in the symptoms and the ocular surface status, respectively. The groups were subdivided into procedures for ocular surface stabilization (A) and visual rehabilitation (B) and those managed conservatively (C). Results: In the subgroup A of group II, an improvement/stabilization of BCVA after punctal cautery (231 eyes), mucous membrane grafting for lid margin keratinization (393 eyes), and fornix reconstruction (28 eyes) was noted in 93.6% of eyes. In subgroup B, all 10 eyes that underwent limbal allograft in group I failed when compared with an improvement of BCVA to better than 20/200 in 65.5% of the 61 eyes that underwent keratoprostheses. It was noted that the limbal status worsened in 66.9% of eyes treated conservatively in group I. Conclusions: Stabilization procedures show a beneficial role while conservative management can lead to deterioration in chronic ocular sequelae of SJS. Keratoprosthesis, specifically the modified osteo-odonto-keratoprosthesis, forms the mainstay for visual rehabilitation in the end-stage disease. This study highlights the improved outcomes with a paradigm shift in the management modalities.

Glaucoma in Modified Osteo-odonto-keratoprosthesis Eyes: Role of Additional Stage 1A and Ahmed Glaucoma Drainage Device–Technique and Timing

PURPOSE To report the technique, timing, and outcomes of the Ahmed glaucoma drainage device in eyes with the modified osteo-odonto-keratoprosthesis (MOOKP) and the role of an additional stage 1A to the Rome-Vienna protocol. DESIGN Retrospective interventional case series. METHODS Case records of 22 eyes of 20 patients with high intraocular pressure at various stages of the MOOKP procedure performed in 85 eyes of 82 patients were studied. Stage 1A, which includes total iridodialysis, intracapsular cataract extraction, and anterior vitrectomy, was done in all eyes as the primary stage. RESULTS Seventeen Ahmed glaucoma drainage devices were implanted in 15 eyes of 14 patients (chemical injury in 9 [10 eyes] and Stevens-Johnson syndrome in 5 patients). Implantation was performed during and after stage 1A in 2 and 7 eyes, respectively, after stage 1B+1C in 1 eye, and after stage 2 in 6 eyes. Eleven of 15 eyes (73.3%) remained stable with adequate control of intraocular pressure over a mean follow-up period of 33.68 months (1-90 months). Complications related to the drainage device were hypotony in 1 eye and vitreous block of the tube in 1 eye. CONCLUSION It is ideal to place the Ahmed glaucoma drainage device prior to the mucosal graft when the anatomy of the ocular surface is least altered with best outcomes. The technique of placement of the drainage device during the various stages of the MOOKP procedure has been described. The intraocular pressure stabilized in three quarters of the eyes with pre-existing glaucoma.

Outcome of allo simple limbal epithelial transplantation (alloSLET) in the early stage of ocular chemical injury

Purpose To analyse the outcome of allo simple limbal epithelial transplantation (alloSLET) in eyes in the early stage following ocular chemical injury to achieve rapid epithelialisation. Patients and methods Records of 18 eyes of 17 patients who underwent alloSLET between April 2013 and Jan 2016 were analysed retrospectively. Patients with grade 4 or worse Duas classification for chemical injury, who presented within a month of the injury or with a non-healing epithelial defect since the injury despite earlier medical or surgical interventions, were included in the study. The time to epithelialisation was the primary outcome measure and the best corrected visual acuity, the clinically assessed epithelial phenotype and symblepharon formation were the secondary outcome measures. Results The mean time to epithelialisation was noted to be 22.5±9.14 days. A best corrected visual acuity of better than 20/120 was achieved in 13 eyes in a mean duration of 33.06+10.73 days following alloSLET. Corneal phenotype with complete epithelialisation was achieved in the immediate postoperative period in 17 of the 18 eyes (94.11%). Seven eyes had a gradual failure of the allograft and 5 eyes underwent subsequent limbal autograft. Symblepharon formation involving one to two quadrants was noted in 3 eyes (16.7%). Conclusions AlloSLET seems to be a useful technique to achieve rapid epithelialisation in severe chemical injuries thereby preventing the adverse effects of delayed epithelial healing. Visual rehabilitative procedures in the chronic phase of chemical injury, in most instances following an alloSLET in the acute stage, did not require keratoplasty, either lamellar or penetrating.

Large lamellar corneoscleral grafts: tectonic role in initial management of severe ocular chemical injuries.

Purpose To report the outcome of large tectonic lamellar grafts in cases of severe chemical injury associated with corneal melt/perforation and scleral ischemia, with or without retinal detachment. Methods This was a retrospective interventional analysis of 7 eyes of 6 patients within 3 months of injury with simultaneous/subsequent surgical procedures to salvage globe integrity. Results Of 7 included eyes, both eyes of one patient underwent phthisical changes. In one eye, the retinal detachment was inoperable; in another, the retina was reattached with silicone oil tamponade, and underwent subsequent Boston type 1 keratoprosthesis with a final best-corrected visual acuity of 20/80 at 3-year follow-up. One eye underwent Lucia type 2 keratoprosthesis, one eye the modified osteo-odonto keratoprosthesis procedure, with visual recovery of 20/120 and 20/80, respectively, and one maintained vision of 20/200 for 2 years following a penetrating keratoplasty. The final best-corrected visual acuity was better than 20/200 in 4 out of these 7 eyes (57.14%). Conclusions In acute severe chemical injuries, corneal perforation with scleral ischemia can threaten globe integrity as well as preclude routine tectonic penetrating procedure. Presence of a concurrent retinal detachment in this setting further complicates the approach as well as the outcome. The use of a large tectonic corneoscleral lamellar graft provides a viable option in the achievement of tectonic stability in these eyes, facilitating future visual rehabilitative procedures.

Scleral necrosis in congenital erythropoietic porphyria: A case report and review of the literature

A 28-year-old presented with complaints of severe pain and redness in the left eye since 2 weeks. He had similar complaints in the right eye 2 years back for which he had undergone a scleral patch graft. Best corrected visual acuity was 20/20 in both eyes. The right had a well vascularized scleral graft and rest of the anterior segment was normal. The left eye had inferior conjunctival congestion with an area of the scleral melt with uveal show just temporal to the limbus in the interpalbebral area. The cornea was clear and anterior chamber was quiet in the left eye. Applanation tonometry and fundus evaluation were normal in both eyes. Physical examination revealed hyperpigmented skin lesion, hypertrichosis and absorption of distal phalanges. Laboratory, ocular and physical findings confirmed the diagnosis of congenital erythropoietic porphyria. He was on oral steroids 40 mg/day since 2 weeks and topical antibiotics and lubricants. He was advised to continue the same and was taken up for scleral patch graft with fibrin glue in the left eye. Postoperatively he was continued on topical and oral steroids and lubricants.3 weeks later the left eye had stabilized however patient came with a melt in the right eye. Since it was an early melt, we went ahead with cyanoacrylate glue and bandage contact lens in the right eye and started him on topical steroids for the right eye also. Three months later both the eyes were stable, and the patient was gradually tapered off the steroids.

Ocular surface cytokine profile in chronic Stevens-Johnson syndrome and its response to mucous membrane grafting for lid margin keratinisation

Background To study the tear cytokine and the conjunctival and oral mucosal marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their alteration following mucous membrane grafting (MMG) for lid margin keratinisation (LMK). Methods In a 1-year prospective study, SJS cases (n=25) and age-matched/sex-matched healthy controls (n=25) were recruited. Tear specimen (Schirmer’s strip), conjunctival and oral mucosal imprints were collected from controls and SJS cases pre-MMG and post-MMG (at first follow-up, n=17). Tear cytokines were profiled using 27-bioplex array. Transforming growth factor-beta (TGF-β)-mediated extracellular matrix changes in conjunctival and oral mucosal cells were analysed by gene expression studies. 30 Results Tear cytokine profiling of chronic SJS cases at pre-MMG stage revealed significant upregulation of cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, IL-1β, monocyte chemoattractant protein-1, IL-15, IL-2, IL-17A and basic fibroblast growth factor (bFGF) with downregulation of IP-10 (interferon gamma-induced protein 10), tumour necrosis factor-α, interferon-γ, IL-10, vascular endothelial growth factor, regulated upon activation normal T-cell expressed and secreted (RANTES), IL-7, IL-12p70 and IL-13, with maximal increase in GM-CSF and maximal downregulation of IP-10, respectively. Of these, IL-2, IL-15, bFGF and IL-17A showed significant correlation with disease severity, pre-MMG. Conjunctival cells pre-MMG showed increase in TGF-β1, TGF-βRII, connective tissue growth factor and collagen-III gene expression by 10, 67, 173 and 184 folds, respectively, which dropped to 1.3, 11, 13.5 and 19 folds correspondingly, post-MMG. However, their expressions in oral mucosa were negligible. Conclusion A proinflammatory, profibrotic, antiapoptotic ocular surface milieu characterises chronic ocular SJS. IP-10, an antifibrotic cytokine was noted to be maximally downregulated, unlike in other forms of chronic dry eye disease. The alterations in the ocular surface are seen to reverse largely with MMG for LMK.

Clinical profile of pythium keratitis: perioperative measures to reduce risk of recurrence

Purpose To report the clinical profile and role of perioperative adjunctive measures to reduce the risk of recurrence in Pythium insidiosum keratitis. Methods Retrospective analysis of 10 eyes of 10 patients with P. insidiosum keratitis. Diagnosis was confirmed by PCR DNA sequencing. Results 7out of 10 patients were from urban locales, and none had any obvious history of injury with vegetative matter and were being treated for fungal keratitis. 6 eyes presented with central full thickness infiltrates with subepithelial and superficial stromal infiltrates radiating in a reticular pattern. Corneal scraping in all eyes revealed sparsely septate fungal-like filaments on potassium hydroxide/Calcofluor. All eyes underwent the first therapeutic penetrating keratoplasty (TPK) based on worsening or non-responsiveness of clinical features to the antifungal regimen. Recurrence was noted in 7 out of 10 eyes of which 2 eyes underwent evisceration. Of the six eyes that underwent cryotherapy following confirmation of microbiological diagnosis of Pythium (along with primary TPK-1, with re-TPK-5), only one eye had a recurrence and had to be eviscerated. Of the two eyes that did not undergo cryotherapy during re-TPK, following microbiological diagnosis, one eye had a recurrence and had to be eviscerated. In two eyes with adjoining scleritis, the host bed was swabbed using absolute alcohol of which one eye was salvaged. Conclusion This series highlights the need to be aware of this entity in the management of refractory fungal keratitis. It also brings to fore the adjunctive measures that could have a beneficial role in the management of pythium keratitis.

Clinico-biochemical correlation of the effect of subconjunctival bevacizumab for corneal neovascularization.

Purpose: The aim of this study was to evaluate the effect of clinical and biochemical effects of subconjunctival bevacizumab injection in eyes with corneal neovascularization (CNV) due to varied etiologies. Methods: This prospective interventional case series included 12 eyes of 12 patients with CNV after failed therapeutic penetrating keratoplasty (4 eyes), viral keratitis (4 eyes), adherent leucoma (2 eyes), and pseudophakic bullous keratopathy (2 eyes). Each eye received 3 doses of 1.25 mg (0.05 mL) of bevacizumab at 1-month intervals. Morphological changes in neovascularization were evaluated at each visit by slit-lamp examination and corneal digital photography. Corneal buttons of 4 eyes that underwent optical penetrating keratoplasty after bevacizumab injections were analyzed for vascular endothelial growth factor (VEGF) expression and were compared with untreated vascularized and normal cadaveric donor corneas. Results: Of the 12 patients, 10 were males and 2 were females. Four eyes received injections in the early phase of vascularization (<12 weeks of onset) of which 3 showed regression of vessels. Eight eyes received bevacizumab in the mature phase (>12 weeks) of which 5 showed regression. The follow-up ranged from 1 to 16 months. Five eyes underwent optical penetrating keratoplasty after receiving the last dose of bevacizumab and maintained graft clarity with no episodes of rejection over a mean follow-up of 9.8 months. Four of these 5 corneal buttons analyzed for VEGF expression revealed clinically significant lower levels of expression as compared with the vascular untreated corneas. No local or systemic adverse effects were noted in any patient. Conclusions: Subconjunctival bevacizumab helps to regress CNV due to a decrease in corneal VEGF levels and might prove beneficial for use in clinical conditions leading to CNV.