Ocular surface changes in patients who have undergone head and neck radiation therapy.

PURPOSE: Dry eye syndrome (DES) is a familiar sequelae of radiation therapy (RT) for head and neck cancers (HNC). Ocular surface changes such as DES occur due to injury to the conjunctival epithelium, goblet cells, corneal surface, lacrimal glands, and meibomian glands. This study aimed at the evaluation and early detection of changes in ocular surface parameters in patients receiving RT for extraocular HNC. METHODS: Forty-two eyes of 21 patients undergoing HNC RT were evaluated. Radiation technique and dose of radiation to the lens and eye were recorded. Subjects were evaluated for meibomian gland changes by meiboscore grading, ocular surface disease index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), and slit-lamp examination before RT, immediately post RT, and 6 weeks post RT. A comparison of the ipsilateral eye on the irradiated side to the contralateral eye was done. RESULTS: A significant reduction in TBUT was seen immediately post RT and 6 weeks post RT ( P < 0.001 and 0.008, respectively), with an increase in meiboscore at both visits ( P < 0.001). An OSDI score of >13 was seen in 23.80% of patients post RT, with a significant difference from baseline ( P < 0.001). On comparing ipsilateral and contralateral eye groups, a significant difference from baseline was seen in TBUT ( P < 0.001 and 0.033, respectively) and meiboscore ( P < 0.001 for both eyes). A significant change of >1 second in TBUT and >1.7 in meiboscore was seen with a mean dose of around 8 Gy to the lens. CONCLUSION: All patients undergoing HNC RT should be followed up for ocular surface and meibomian gland changes. The contralateral eye should also be evaluated. Patients receiving lower doses to the ocular structures should also be kept under follow-up.

Corneal edema associated with degenerating Soemmering ring cataract: Clinical-pathologic correlation.

Purpose: To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract. Observations: We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified Soemmering ring cataract. Histopathological examination demonstrated extracellular calcific deposits compatible with cataractous lens material on the posterior surface of stripped Descemet membrane of two patients. The deposits were associated with prominent localized loss of corneal endothelium and were not associated with inflammation. Morphologically similar acellular material was identified in the biopsied aqueous and vitreous fluid of one patient. Management included endothelial keratoplasty, anterior chamber lavage, pars plana vitrectomy, aspiration/removal of a portion of Soemmering ring cataract without intraocular lens implant explantation, and the removal of the entire capsular bag/implant complex. Cornea cleared and visual acuity improved in both patients who underwent endothelial keratoplasty. Persistent elevated intraocular pressure led to visual deterioration in one patient with secondary glaucoma. Conclusions and Importance: Dispersion of calcific Soemmering ring cataract can occur decades following cataract surgery leading to corneal edema, secondary glaucoma, and vitreous opacities. Timely recognition of this phenomenon may prevent ocular morbidity, including corneal edema and glaucoma.

Allograft rejection after living-related simple limbal epithelial transplantation.

A 23-year-old man presented with congestion, peripheral corneal vascularization, an elevated ridge-like epithelial line and cellular infiltration around limbal transplants, 15 months after undergoing living-related simple limbal epithelial transplantation (SLET) for total limbal stem cell deficiency. A diagnosis of acute allograft rejection was made and he was treated with intravenous methylprednisolone, topical and oral prednisolone as well as systemic cyclosporine and azathioprine, leading to reversal of the signs. Similar findings were noted during a later rejection episode. An epithelial rejection line and cellular infiltration of limbal transplants are easily identifiable clinical signs of allograft rejection post SLET.

Minor salivary gland transplantation for severe dry eye disease due to cicatrising conjunctivitis: multicentre long-term outcomes of a modified technique.

AIM: To report the clinical outcomes of autologous minor salivary gland transplantation (MSGT) for the treatment of severe dry eye disease caused by cicatrising conjunctivitis. METHODS: This was a retrospective case series of patients undergoing MSGT at four different centres from 2016 to 2018. The technical modifications included en bloc harvesting of a 20 mm×15 mm mucosa-gland-muscle complex and fixation of the glands to the superior bulbar surface anchored to the superior rectus muscle. The primary outcome measure was improvement in best-corrected visual acuity (BCVA). Secondary outcome measures were change in Schirmer test scores and grades of conjunctival and corneal fluorescein staining, grades of corneal neovascularisation, opacification and keratinisation. RESULTS: 21 eyes of 19 patients underwent MSGT, with a median follow-up duration of 3 years. The median BCVA improved from a baseline value of 20/500 to 20/125 at 1 year (p=0.0004) and 20/80 at 3 years (p=0.0002) after surgery. The proportion of cases with BCVA ≥20/200 improved from 38% at baseline to 67% at 1 year (p=0.0294), 78% at 2 years (p=0.0227) and 93% at 3 years (p=0.0015) after surgery. There was a significant improvement (p<0.0036) in Schirmer scores, conjunctival and corneal staining scores as well as grades of corneal neovascularisation and opacification after surgery. There were no serious sight-threatening complications in the transplanted eyes or at the donor site. CONCLUSIONS: Long-term improvement in the visual acuity, ocular surface environment, and keratopathy was noted after MSGT performed in severely dry eyes using a modified technique.

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

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.

Systemic Immunosuppression for Limbal Allograft and Allogenic Limbal Epithelial Cell Transplantation.

Bilateral limbal stem cell deficiency (LSCD) treatment requires the need to obtain allogenic limbal tissue for transplantation. Outcomes of different surgical techniques depend on multiple factors, including the underlying etiology, ocular surface, eyelid status and used surgical intervention. Some of the management options for bilateral LSCD include cadaveric, living related or living non-related conjunctival limbal allograft (CLAL), keratolimbal allograft (KLAL), allogenic cultured limbal epithelial transplantation (CLET) and allogenic simple limbal epithelial transplantation (SLET). Systemic immunosuppressive therapy plays a pivotal role in survival of transplanted tissue. The present review focuses on different systemic immunosuppression protocols for limbal allograft and allogenic limbal epithelial cell transplantation, with specific emphasis on different surgical techniques and their outcomes. We included all reports with details of different systemic immunosuppression protocols for limbal allograft and allogenic limbal epithelial cell transplantation. Oral cyclosporine A at different doses is the most commonly used immunosuppressive agent in limbal allograft and allogenic limbal epithelial cell transplantation. However, different studies using oral mycophenolate mofetil and tacrolimus also reported good results. In conclusion, systemic immunosuppression protocols for limbal allograft and allogenic limbal epithelial cell transplantation are not standardized. Further studies regarding different surgical techniques should assess outcomes and adverse effects of such protocols.

Limbal Stem Cell Deficiency-Demography and Underlying Causes.

PURPOSE: To determine the demographic features of patients affected by limbal stem cell deficiency (LSCD), and to identify the underlying causes of LSCD. DESIGN: Retrospective, multicenter case series. SETTING: Two large tertiary care ophthalmology hospitals. SUBJECTS: Patients with a diagnosis of LSCD presenting from January 1, 2005 to December 31, 2014. METHODS: Records of patients with a clinical diagnosis of LSCD were reviewed. Demographic details and clinical features at presentation, as well as the underlying cause of LSCD (if identified), were noted. Descriptive statistical analysis and chart preparation were done. Main outcome measures were type of LSCD (unilateral or bilateral), age and sex of patients, extent of LSCD (clock hours of limbus involved), and underlying cause of LSCD. RESULTS: We found 1331 patients with LSCD in the 10-year period under study. Unilateral LSCD was more common (791 patients) than bilateral LSCD (540 patients). Out of 1331 patients, 875 (65.74%) were male. The median age of patients was 24 years. Extent of LSCD could be determined in 1849 eyes, of which 1239 eyes (67.00%) had total LSCD. The underlying cause of LSCD could be identified in 1512 eyes. In cases of unilateral LSCD, ocular surface burns was the commonest identifiable cause (83.73%). The leading identifiable causes of bilateral LSCD were ocular surface burns (29.95%), allergic conjunctivitis (29.48%), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (23.11%), aniridia (9.43%), and mucous membrane pemphigoid (3.54%). Lime ("chuna") injury was responsible for ocular surface burns in 352 out of 567 cases in which the agent was identified (62.08%). CONCLUSIONS: In our study, unilateral LSCD was more common than bilateral LSCD. Young male subjects were commonly affected, with a majority of eyes suffering from total LSCD. Overall, ocular surface burns are the leading cause of LSCD. Unilateral and bilateral LSCD had a markedly different distribution of causes, necessitating different approaches to management.

Surgical Management of Bilateral Limbal Stem Cell Deficiency.

Limbal stem cell deficiency (LSCD) is now established as a distinct entity with a spectrum of clinical manifestations. Bilateral LSCD presents a unique set of challenges to the clinician dealing with ocular surface disease, due to the underlying causes, clinical presentation, and adnexal status, as well as lack of a source of autologous limbal stem cells. Various surgical modalities have been described to achieve visual rehabilitation in patients with bilateral LSCD. These can primarily be divided into cell-based therapies and implantation of keratoprostheses. In this review, the surgical options for management of bilateral LSCD, including autologous and allogeneic cell-based therapies and different types of keratoprostheses are described and classified. The indications, prerequisites, technique, results and complications of each modality are discussed. Based on the status of the ocular surface, an algorithm for choosing appropriate surgical management for vision restoration in bilateral LSCD has been proposed.

Autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency: multicentre results.

PURPOSE: To report outcomes of autologous simple limbal epithelial transplantation (SLET) performed for unilateral limbal stem cell deficiency (LSCD) at multiple centres worldwide. METHODS: In this retrospective, multicentre, interventional case series, records of patients who had undergone autologous SLET for unilateral LSCD, with a minimum of 6 months of follow-up, were reviewed. The primary outcome measure was clinical success, defined as a completely epithelised, avascular corneal surface. Kaplan-Meier survival curves were constructed and survival probability was calculated. A Cox proportional hazards analysis was done to assess association of preoperative characteristics with risk of failure. Secondary outcome measures included the percentage of eyes achieving visual acuity of 20/200 or better, percentage of eyes gaining two or more Snellen lines and complications encountered. RESULTS: 68 eyes of 68 patients underwent autologous SLET, performed across eight centres in three countries. Clinical success was achieved in 57 cases (83.8%). With a median follow-up of 12 months, survival probability exceeded 80%. Presence of symblepharon (HR 5.8) and simultaneous keratoplasty (HR 10.8) were found to be significantly associated with a risk of failure. 44 eyes (64.7%) achieved a visual acuity of 20/200 or better, and 44 eyes (64.7%) gained two or more Snellen lines. Focal recurrences of pannus were noted in 21 eyes (36.8%) with clinical success. CONCLUSION: Autologous SLET is an effective and safe modality for treatment of unilateral LSCD. Clinical success rates and visual acuity improvement are equal to or better than those reported with earlier techniques.

Efficacy of conjunctival resection with cyanoacrylate glue application in preventing recurrences of Mooren's ulcer.

AIM: To evaluate the role of conjunctival resection along with cyanoacrylate glue and bandage contact lens application in preventing recurrences and arresting progression in cases of Mooren's ulcer. METHOD: This retrospective interventional case series included cases of Mooren's ulcer that underwent conjunctival resection with cyanoacrylate glue and bandage contact lens application between 2011 and 2014. Systemic immunosuppression was initiated depending on the laterality and severity of disease. The primary outcome measures were clinical quiescence and recurrence-free survival. Kaplan-Meier plots were constructed and survival analysis done using the R software environment for statistical analysis. Secondary outcome measures were needed for systemic immunosuppression, change in best-corrected visual acuity and complications encountered. RESULTS: We evaluated 16 eyes of 12 patients who presented to us during the study period. The mean follow-up duration was 9.6 months. All eyes achieved clinical quiescence with a median recurrence-free survival of 141 days. The Kaplan-Meier survival curve showed probability of recurrence-free survival to be 42.5% at 1 year, which further dropped down to 21.3% at 2 years. All patients with recurrence (seven eyes of four patients) required systemic immunosuppression. CONCLUSIONS: Conjunctival resection and cyanoacrylate glue application are not effective in avoiding recurrences and halting the disease progression in cases of Mooren's ulcer. Systemic immunosuppression remains the mainstay of therapy.

Multidrug-Resistant Pseudomonas aeruginosa Keratitis: Risk Factors, Clinical Characteristics, and Outcomes.

PURPOSE: To identify risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) keratitis and to report clinical characteristics and outcomes of this infection. DESIGN: Retrospective, case-control study. PARTICIPANTS: Ninety episodes of P. aeruginosa keratitis from a tertiary care eye institution from 2007 through 2014 were identified. Episodes of MDR-PA keratitis were taken as cases. Episodes of drug-sensitive P. aeruginosa keratitis during the same period were taken as controls. METHODS: Chart review of cases and controls. Multidrug resistance was defined as resistance to 3 or more classes of antimicrobial drugs. Logistic regression analysis was used to determine association of baseline characteristics with multidrug resistance. Clinical characteristics and risk factors in each group also were compared. MAIN OUTCOME MEASURES: Risk factors for multidrug resistance, including age, gender, eye, duration of symptoms, topical steroid or lubricant ointment use, trauma, prior ocular surgery, presence of a compromised ocular surface, and bandage contact lens use. RESULTS: Twenty-three episodes of MDR-PA keratitis (cases) and 67 episodes of drug-sensitive P. aeruginosa keratitis (controls) were identified. In the multivariate analysis, lubricant ointment use, presence of a compromised ocular surface, and bandage contact lens use were associated with MDR-PA keratitis. Antimicrobial resistance in the MDR-PA keratitis isolates was least for colistin and imipenem (56.52% each). Corneal perforation was more common in cases (52.17% [12 of 23]) than in controls (11.94% [8 of 67]; P = 0.0001). Cyanoacrylate glue application was required in 47.82% of cases (11 of 23), compared with 22.38% of controls (15 of 67; P = 0.031). Keratoplasty was more commonly required in cases (47.82% [11 of 23]) than in controls (20.89% [14 of 67]; P = 0.017). CONCLUSIONS: Lubricant ointment use, a compromised ocular surface, and bandage contact lens use are associated with MDR-PA keratitis. Preservative-free lubricant ointment may act as a source or reservoir of infection. Outcomes are worse in MDR-PA keratitis compared with drug-sensitive P. aeruginosa keratitis.

Customised simple limbal epithelial transplantation for recurrent limbal stem cell deficiency.

A 4-year-old boy developed unilateral, total limbal stem cell deficiency (LSCD) following an acid injury. A stable ocular surface was achieved with autologous simple limbal epithelial transplantation (SLET), performed 4 months after the injury. Focal areas of conjunctivalisation were noted in the postoperative period. These were addressed using a novel modification of SLET. A very small piece of limbus from the healthy eye was split into multiple pieces, and applied to the bare corneal stroma with fibrin glue after pannus resection. The surface was covered with amniotic membrane. This resulted in a stable surface, and visual acuity improved to 20/50. The donor remained healthy despite two biopsies being harvested. This case demonstrates that early ocular surface reconstruction may be considered in children with LSCD if amblyopia is a concern. Customised SLET allows surgeons to tackle focal recurrences of LSCD effectively, using minimal limbal tissue from the donor site.

Optical coherence tomography findings and retinal changes after vitrectomy for optic disc pit maculopathy.

PURPOSE: To study the optical coherence tomography (OCT) patterns in optic disc pit maculopathy and retinal changes after vitreous surgery. MATERIALS AND METHODS: Retrospective review of consecutive cases with optic disc pit maculopathy seen at two tertiary eye institutes from January 2005 to June 2009. RESULTS: Twenty-four eyes of 23 patients are included. The presenting visual acuity ranged from 20/400 to 20/20 (median:20/80). The median age at presentation was 24 years (range, 6-57 years). Optical coherence tomography demonstrated a combination of retinoschisis and outer layer detachment (OLD) in 19 (79.17%) eyes, OLD only in 3 (12.5%) eyes and retinoschisis only in 2 (8.33%) eyes. An obvious communication (outer layer hole) between the schisis and OLD was seen in 14 (73.68%) of the 19 eyes with both features. Of the 21 eyes with retinoschisis, schisis was present in multiple layers in 15 (71.43%) and single layer in 6 (28.57%) eyes. Eleven eyes underwent pars plana vitrectomy including creation of posterior vitreous detachment (PVD), fluid-air exchange, low intensity laser photocoagulation at the temporal edge of the optic disc pit and non-expansile perfluoropropane gas (14%) injection. Five (45.45%) of 11 eyes undergoing vitrectomy had complete resolution and 4 (36.36%) eyes had partial resolution of maculopathy. Visual acuity improved in 8 (72.72%) of 11 eyes. CONCLUSION: Optical coherence tomography demonstrates multiple layer schisis and outer layer detachment as main features of optic disc pit maculopathy. Vitrectomy with PVD induction, laser photocoagulation and gas tamponade results in anatomical and visual improvement in most cases with optic disc pit maculopathy.

Unilateral partial limbal stem cell deficiency: contralateral versus ipsilateral autologous cultivated limbal epithelial transplantation.

PURPOSE: To report the outcomes of autologous cultivated limbal epithelial transplantation using the healthy part of the affected eye or the fellow eye as a source of limbal stem cells in patients with unilateral, partial limbal stem cell deficiency (LSCD). DESIGN: Retrospective, nonrandomized, interventional case series. METHODS: setting: L. V. Prasad Eye Institute, Hyderabad, India. study population: Patients with unilateral, partial LSCD who underwent autologous cultivated limbal epithelial transplantation between 2001 and 2011. intervention: The limbal biopsy was taken either from the healthy part of the limbus of the same eye (ipsilateral group) or from the healthy fellow eye (contralateral group). Cells were cultivated using a xeno-free explant culture technique, and cultivated cells were transplanted onto the affected surface. primary outcome measure: Success of cultivated limbal epithelial transplantation, defined as a completely epithelialized, avascular, and clinically stable corneal surface. RESULTS: Seventy eyes of 70 patients were studied. The mean follow up was 17.5 ± 7 months. In 34 eyes the limbal biopsy was taken from the ipsilateral eye and in the remaining 36 eyes from the contralateral eye. Clinical success was achieved in 70.59% of eyes in the ipsilateral group and 75% of eyes in the contralateral group (P = .79). Limbal transplant survival rates at the final follow-up visit were 65.1% ± 0.09% in the ipsilateral group and 53.6% ± 0.12% in the contralateral group (P = .74). CONCLUSIONS: Ocular surface restoration in partial LSCD is possible with cell-based therapy. Outcomes are similar irrespective of whether the limbal biopsy is taken from the healthy part of the ipsilateral eye or the contralateral eye.

Cross-linking for microbial keratitis.

The success of collagen cross-linking as a clinical modality to modify the clinical course in keratoconus seems to have fueled the search for alternative applications for this treatment. Current clinical data on its efficacy is limited and laboratory data seems to indicate that it performs poorly against resistant strains of bacteria and against slow growing organisms. However, the biological plausibility of crosslinking and the lack of effective strategies in managing infections with these organisms continue to focus attention on this potential treatment. Well-conducted experimental and clinical studies with controls are required to answer the questions of its efficacy in future.

Successful simple limbal epithelial transplantation (SLET) in lime injury-induced limbal stem cell deficiency with ocular surface granuloma.

A 9-year-old boy presented with unilateral, total limbal stem cell deficiency (LSCD) complicated by the presence of a large fibro-vascular ocular surface mass lesion secondary to accidental lime injury. The pathological tissue covering the cornea was excised and simple limbal epithelial transplantation (SLET) was performed using autologous limbal tissue from the fellow eye. Histopathology of the excised ocular surface tissue revealed exuberant granulation tissue interspersed with retained calcium particles. At 6 weeks postoperatively, a focal recurrence of LSCD with symblepharon and forniceal shortening was noted superiorly. This was successfully managed by performing conjunctival autografting along with supplemental SLET. The unaided vision had improved from light perception at presentation to 20/40 at 6 months postoperatively. The fornices were deep and the corneal surface was avascular, epithelised and stable. This case demonstrates the efficacy of SLET in a child with severe ocular burns, highlighting the role of supplementary procedures customised to treat focal recurrences of LSCD.

Role of topical, subconjunctival, intracameral, and irrigative antibiotics in cataract surgery.

PURPOSE OF REVIEW: To summarize current understanding of antibiotic prophylaxis in cataract surgery, with particular emphasis on available evidence and change in practice patterns over the past decade. RECENT FINDINGS: Povidone-iodine application prior to cataract surgery remains a universal practice, and is backed by good quality evidence. Subsequent to the results of the European multicenter trial documenting decreased risk of endophthalmitis with intracameral cefuroxime injection at the end of surgery, similar benefit with intracameral antibiotic use has been reported in studies with large sample sizes from multiple centers around the world. There has been a distinct change in practice patterns in many countries, with intracameral antibiotic use becoming part of routine protocol. In the USA, topical fluoroquinolone application remains the most popular mode of antibiotic prophylaxis. A promising approach is the development of novel drug delivery methods like polymeric devices designed for sustained antibiotic release. SUMMARY: Based on current evidence, the recommended measures for endophthalmitis prophylaxis are preoperative topical instillation of povidone-iodine and intracameral antibiotic injection at the end of cataract surgery.