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.

Autologous serum eye drops in dry eye disease: Preferred practice pattern guidelines.

Autologous serum eye drops provide lubrication and promote epithelial healing. They have been successfully used in the management of ocular surface disorders such as dry eye disease, persistent epithelial defects and neurotrophic keratopathy for many decades. A great deal of variation in the methods of preparation of autologous serum eye drops, the end concentration and the duration of use exists in published literature. In this review, simplified recommendations for preparation, transport, storage and use of autologous serum are described. Evidence for the use of this modality in aqueous deficient dry eye disease is summarized, along with expertise-based rationale.

Peripheral Ulcerative Keratitis as a Manifestation of Drug-Induced Cicatrizing Conjunctivitis.

Ocular surface drug toxicity due to the long-term use of topical medication is a commonly overlooked cause of chronic conjunctival inflammation. A variety of eye drops, including but not limited to anti-glaucoma medications can cause drug-induced cicatrizing conjunctivitis. The classical descriptions of this condition include inflammation and scarring involving the eyelids, puncta, and conjunctiva. Herein, we present a case with bilateral peripheral ulcerative keratitis as a manifestation of drug-induced cicatrizing conjunctivitis.

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.

Allergic conjunctivitis in children: current understanding and future perspectives.

PURPOSE OF REVIEW: The rising global burden of allergic diseases, particularly in the pediatric population, is of serious concern. Ocular allergy is one of the most common ocular pathologies met in clinical practice. A large proportion of children and adolescents suffer from allergic eye diseases (AEDs), which affect their quality of life. The available treatments and surgical modalities have their limitations and side effects. Therefore, the development of novel and alternate strategies is the need of the hour and requires a timely review of currently available knowledge. RECENT FINDINGS: The current review covers the incidence and prevalence of AEDs, factors influencing occurrence and severity of AED (age, sex, socioeconomic status etc.), underlying mechanisms, role of allergy testing and immunotherapy in children, development of diagnostic markers and novel therapies including cells and molecules. SUMMARY: Understanding the demographics, clinical patterns and risk factors of AED can help formulate appropriate preventive and therapeutic strategies for the effective management of this common cause of ocular morbidity. The future therapeutics for AED seems to rely primarily on cells (mesenchymal stem cells, Tregs, mast cells), cell products, molecules with immunosuppressive potential and immunotherapy.

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.

Corneal endothelial alterations in alcohol dependence syndrome.

BACKGROUND/AIMS: To evaluate the corneal endothelial changes in patients with alcohol dependence syndrome (ADS). METHODS: A total of 322 corneas of 322 subjects were studied, and two groups were formed. The first, the ADS group, included 161 corneas of 161 patients and the second, the age-matched control group, was composed of 161 corneas of 161 healthy subjects. Both the groups were examined by specular microscope and the endothelial parameters were compared. The endothelial parameters were also compared before and after the abstinence of alcohol in the former group. The ADS group was further analysed to assess the influence of life time alcohol consumption, years/pattern of drinking, levels of Liver enzymes, levels of mean corpuscular volume, screening questionnaires and stages of fatty liver on corneal endothelium. RESULTS: On comparing the two groups using Mann-Whitney U test, a significant difference was found in central corneal thickness (CCT) and endothelial cell density (CD) between the ADS (CCT: 529±29 µm, CD: 2571±236 cells/mm2) and control groups (CCT: 510±32 µm, CD: 2752±291 cells/mm2) (P<0.001 (CCT); P<0.001 (CD)). Using Wilcoxon sign-rank test, a significant difference was found in CCT (P<0.001) and CD (P<0.001) with abstinence of alcohol. Kruskal-Wallis test was used to compare the endothelial parameters in four stages of fatty liver and found a significant difference in terms of CCT (P<0.001) and CD (P<0.001). CONCLUSIONS: Corneal endothelial alteration is present in patients with ADS, more marked in patients with an increase in stage of fatty liver.

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.

Conjunctival pedicle flap in management of open globe injury with corneal tissue loss.

Accidental injury with scissors led to an open globe injury with iris prolapse and corneal tissue loss in the right eye of a 15-year-old girl. Attempts to suture the laceration normally, led to persistent aqueous leak, and tight suturing was leading to unacceptable distortion of the corneal contour. In the absence of donor tissue or tissue glue, a bulbar conjunctival pedicle flap was used to augment sutures placed without undue tension, and watertight closure of the globe was achieved. Postoperatively, the flap retracted, and excellent tectonic, cosmetic and refractive outcomes were achieved. A conjunctival pedicle flap can be a useful adjunct in the armamentarium of the corneal surgeon while dealing with open globe injuries with corneal tissue loss.

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.