Corneal stromal changes following simple limbal epithelial transplantation on Scheimpflug densitometry: Early results.

CONTEXT: Chemical injury to eyes causes limbal stem cell deficiency (LSCD), which leads to conjunctival epithelium and underlying stromal changes. Simple limbal epithelial transplant helps to restore corneal epithelium and corneal stromal clarity. These changes are documented in this prospective eye study. PURPOSE: To report the changes in epithelial/stromal (E/S) reflectivity ratio and corneal stromal densitometry following simple limbal epithelial transplantation (SLET) in patients with unilateral chemical burn-induced LSCD. METHODS AND MATERIAL: It is a prospective imaging study of cornea before and after SLET. Corneal densitometry with Pentacam and epithelial and stromal reflectivity on anterior segment optical coherence tomography were analyzed for five patients (n = 5 eyes), who underwent autologous SLET for unilateral chemical burn-induced LSCD. STATISTICAL ANALYSIS USED: Mann-Whitney U-test and Pearson correlation. RESULTS: A significant improvement in E/S reflectivity was noted at 1 month (P < 0.05) after SLET, and this was maintained until the end of 6 months. The densitometry measurements decreased in the entire cornea at every level, that is, anterior, central, and posterior cornea. However, the values did not normalize till the last follow-up at 6 months. CONCLUSIONS: A trend of normal corneal epithelization exists in eyes undergoing SLET. Densitometry at all the levels, the anterior, central, and posterior cornea, also decreases after SLET. SLET improves visual outcomes in LSCD eyes not only by epithelization but also by reducing stromal scarring.

Kuragel: A biomimetic hydrogel scaffold designed to promote corneal regeneration.

Cornea-related injuries are the most common cause of blindness worldwide. Transplantation remains the primary approach for addressing corneal blindness, though the demand for donor corneas outmatches the supply by millions. Tissue adhesives employed to seal corneal wounds have shown inefficient healing and incomplete vision restoration. We have developed a biodegradable hydrogel - Kuragel, with the ability to promote corneal regeneration. Functionalized gelatin and hyaluronic acid form photo-crosslinkable hydrogel with transparency and compressive modulus similar to healthy human cornea. Kuragel composition was tuned to achieve sufficient adhesive strength for sutureless integration to host tissue, with minimal swelling post-administration. Studies in the New Zealand rabbit mechanical injury model affecting corneal epithelium and stroma demonstrate that Kuragel efficiently promotes re-epithelialization within 1 month of administration, while stroma and sub-basal nerve plexus regenerate within 3 months. We propose Kuragel as a regenerative treatment for patients suffering from corneal defects including thinning, by restoration of transparency and thickness.

In vitro Assay to Examine the Function of Tears on Corneal Epithelial Cells.

Tears contain numerous secreted factors, enzymes, and proteins that help in maintaining the homeostatic condition of the eye and also protect it from the external environment. However, alterations to these enzymes and/or proteins during pathologies such as mechanical injury and viral or fungal infections can disrupt the normal ocular homeostasis, further contributing to disease development. Several tear film components have a significant role in curbing disease progression and promoting corneal regeneration. Additionally, several factors related to disease progression are secreted into the tear film, thereby serving as a valuable reservoir of biomarkers. Tears are readily available and can be collected via non-invasive techniques or simply from contact lenses. Tears can thus serve as a valuable and easy source for studying disease-specific biomarkers. Significant advancements have been made in recent years in the field of tear film proteomics, lipidomics, and transcriptomics to allow a better understanding of how tears can be utilized to gain insight into the etiology of diseases. These advancements have enabled us to study the pathophysiology of various disease states using tear samples. However, the mechanisms by which tears help to maintain corneal homeostasis and how they are able to form the first line of defense against pathogens remain poorly understood and warrant detailed in vitro studies. Herein, we have developed an in vitro assay to characterize the functional importance of patient isolated tears and their components on corneal epithelial cells. This novel approach closely mimics real physiological conditions and could help the researchers gain insight into the underlying mechanisms of ocular pathologies and develop new treatments. Key features • This method provides a new technique for analyzing the effect of tear components on human corneal epithelial cells. • The components of the tears that are altered in response to diseases can be used as a biomarker for detecting ocular complications. • This procedure can be further employed as an in vitro model for assessing the efficacy of drugs and discover potential therapeutic interventions.

Management of cataract in dry eye disease: Preferred practice pattern guidelines.

Cataract surgery is one of the most commonly performed ophthalmic surgeries in the world. Dry eye disease (DED) is found to coexist in most patients with cataracts due to the overlapping age groups of both these conditions. Preoperative evaluation for DED is important to improve outcomes. A pre-existing DED affecting the tear film is likely to affect biometry. Moreover, special intraoperative considerations are needed in eyes with DED to reduce complications and improve postoperative outcomes. Dry eye disease (DED) is known to occur following an uneventful cataract surgery or a pre-existing DED is likely to worsen following cataract surgery as well. In these situations, despite a good visual outcome, patient dissatisfaction is common owing to the distressing DED symptoms. This review aims to summarize the preoperative, intraoperative, and postoperative considerations when performing cataract surgery in the presence of a coexisting DED.

Efficacy and safety of 0.05% micellar nano-particulate (MNP) cyclosporine ophthalmic emulsion in the treatment of moderate-to-severe keratoconjunctivitis sicca: a 12-week, multicenter, randomized, active-controlled trial.

BACKGROUND: Keratoconjunctivitis sicca or dry eye disease (DED) is a multifactorial disorder underpinned by a complex inflammatory cycle. Introduction of topical cyclosporine has been a significant advance in the management of DED. In recent years advancements in formulation technology have led to development of micellar nano-particulate (MNP) cyclosporine formulations that promise better penetration into ocular target tissues and potential for reduced ocular surface irritation. METHODS: We compared two dosing regimes of a proprietary MNP cyclosporine emulsion with the widely marketed topical cyclosporine formulation Restasis™ in a multicenter parallel-group randomised trial in patients with DED. Patients were randomised to one of 3 treatment groups with 90 patients eligible for the per protocol analysis: 30 in the higher dose test arm A; 32 in the lower dose test arm B; and 28 in the Restasis™ control arm C. All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group at 12 weeks, using the Student's t test. Wilcoxon's rank sum test was used to test individual symptom scores and clinician's global evaluation of treatment grades. RESULTS: Corneal fluorescein staining score, the primary efficacy endpoint, decreased by 6.8 ± 4.0, 5.7 ± 3.9, and 4.6 ± 3.6 points in the 3 groups respectively, indicating superior efficacy in test arm A in comparison to control arm C (p = 0.0026). Schirmer's tear test, conjunctival lissamine staining score, ocular surface disease index, and individual dry eye symptom scores also favoured higher dose MNP cyclosporine over Restasis™. The study failed to differentiate the treatment arms in terms of clinician's global evaluation of treatment, use of tear substitutes, best corrected visual acuity or safety and toleration. CONCLUSION: The results indicate that the dose of 1 drop of a 0.05% w/v ophthalmic emulsion of MNP cyclosporine administered topically twice daily yields better outcomes at 12 weeks than the lower dose tested in the study, and is more efficacious than an equivalent dose of Restasis™, the active control used in the study. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Registry of India on 29/03/2019, and was assigned registration number CTRI/2019/03/018319.

Corneal stem cells niche and homeostasis impacts in regenerative medicine; concise review.

The limbal stem cells niche (LSCN) is an optimal microenvironment that provides the limbal epithelial stem cells (LESCs) and strictly regulates their proliferation and differentiation. Disturbing the LSCN homeostasis can lead to limbal stem cell dysfunction (LSCD) and subsequent ocular surface aberrations, such as corneal stromal inflammation, persistent epithelial defects, corneal neovascularisation, lymphangiogenesis, corneal opacification, and conjunctivalization. As ocular surface disorders are considered the second main cause of blindness, it becomes crucial to explore different therapeutic strategies for restoring the functions of the LSCN. A major limitation of corneal transplantation is the current shortage of donor tissue to meet the requirements worldwide. In this context, it becomes mandatory to find an alternative regenerative medicine, such as using cultured limbal epithelial/stromal stem cells, inducing the production of corneal like cells by using other sources of stem cells, and using tissue engineering methods aiming to produce the three-dimensional (3D) printed cornea. Limbal epithelial stem cells have been considered the magic potion for eye treatment. Epithelial and stromal stem cells in the limbal niche hold the responsibility of replenishing the corneal epithelium. These stem cells are being used for transplantation to maintain corneal epithelial integrity and ultimately sustain optimal vision. In this review, we summarised the characteristics of the LSCN and their current and future roles in restoring corneal homeostasis in eyes with LSCD.

Surgical Management of Peripheral Ulcerative Keratitis: Update on Surgical Techniques and Their Outcome.

Peripheral ulcerative keratitis (PUK) is an inflammatory, necrotic condition in the peripheral cornea which may end in corneal perforation and visual morbidity if not treated adequately. PUK can occur due to infectious or non-infectious causes. Early cases need medical therapy, both locally and systemically (for some cases). However, advanced PUK may necessitate surgical removal of inciting cause of the pathology and maintaining tectonic stability. Such surgical treatment, including corneal transplantations, may be used in an emergency setting or for visual rehabilitation following preliminary stabilization of the affected cornea. The outcome of these surgeries need to be analyzed to understand the long-term visual prognosis of such eyes. This is an attempt to analyze surgical modalities in the management of PUK and their outcomes.

Glaucoma Evaluation and Management in Eyes With Boston Type 1 and Aurolab Keratoprostheses in an Indian Cohort.

PURPOSE: The purpose of this study was to evaluate glaucoma and its management in eyes with Boston type 1 keratoprosthesis (Boston-Kpro) and Aurolab keratoprosthesis (Auro-Kpro) in an Indian cohort. METHODS: This retrospective comparative case series included 175 eyes of 175 patients who underwent type 1 keratoprosthesis from 2009 until 2017; type 1 Boston-Kpro was performed in 107 eyes (107 patients) and Auro-Kpro in 68 eyes (68 patients). The eyes with <1-month follow-up were excluded, and hence, for the analysis of glaucoma, 62 eyes with Auro-Kpro and 99 eyes with Boston-Kpro were included. Progression was defined as the worsening of optic disc damage/progression by visual field/uncontrolled IOP needing additional medications or glaucoma surgery. RESULTS: The post-Kpro mean follow-up was 1.8 ± 1.7 years. After Kpro, overall glaucoma was noted in 61% of eyes (98/161). Preexisting glaucoma was noted in 28% of eyes (45/161), postoperative glaucoma was noted in 33% of eyes (53/161), and 39% of eyes (63/161) did not have glaucoma. Among those with preexisting glaucoma, 49% of eyes (22/45) progressed after Kpro implantation. The proportion of eyes with glaucoma in Auro-Kpro (56.5% of eyes) and Boston-Kpro (63.6% of eyes) was similar (P = 0.46). The Kaplan-Meier curve for cumulative survival (Kpro-retention rate) was similar in eyes with and without glaucoma (83% vs. 76% at 1 year, 72% vs. 70% at 2 years; P = 0.65). A higher number of prior intraocular surgeries (P = 0.04) was significantly associated with risk for postoperative glaucoma. CONCLUSIONS: Glaucoma was seen in more than half of the eyes with type 1 keratoprosthesis. The presence of glaucoma did not seem to affect the retention of keratoprosthesis. A high rate of postoperative glaucoma and the progression of preexisting glaucoma need close monitoring and appropriate management.

Clinical Aspects of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis With Severe Ocular Complications in India.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of rare, severe immunological blistering skin reactions which are triggered by medication intake or infections. The acute phase is characterized by necrolysis of the skin and desquamation of mucosa, primarily oral and ocular, with significant mortality rates. The chronic phase is characterized by multi-organ sequelae with increased rates of morbidity and reduced quality of life for patients who have survived the acute phase. Since the primary goal in the acute phase is saving the life of the patient, ocular involvement is often missed and a significant proportion of patients present to an ophthalmologist with the chronic ocular sequelae. In India, chronic ocular sequelae and low vision are observed in two-thirds of patients who present in the chronic phase of SJS/TEN. In the chronic phase of ocular involvement, there are definite windows of opportunity which if targeted with specific interventions such as scleral lenses and mucous membrane grafts can help reduce the incidence of corneal blindness and improve the quality of life for patients with SJS/TEN. Over the last decade, several studies from India have advanced the understanding of the natural course of ocular involvement in SJS/TEN and the outcomes of timely interventions in the chronic phase of the disease. We present an overview of the epidemiology of ocular complications of SJS/TEN in India, the specific challenges faced in the management of ocular complications in the acute stage and recent advances in management of the chronic ocular complications of the disease.

Mini-Review: Regenerating the Corneal Epithelium With Simple Limbal Epithelial Transplantation.

Simple limbal epithelial transplantation (SLET) is an ingenious, low cost and effective technique of limbal stem cell transplantation (LSCT) that is increasingly being undertaken in practice across the world. Since it was first described a decade ago, the technique has been performed in a variety of cases of limbal stem cell deficiency (LSCD) and has underwent several innovative modifications. Published literature on SLET has progressively increased over time and successful outcomes in various clinical scenarios have been reported. This concise review attempts to present a crisp account of SLET covering the indications and contraindications of performing the procedure; detailed account of pre-operative work up and preparation; surgical technique and its modifications; post-operative course, care and possible complications as well as published outcomes of surgery from across the world. Comparative analysis of various techniques of LSCT have been discussed and common concerns of surgeons practising or those who are planning to start practising SLET have been addressed. The authors hope that the pragmatic insights and pearls given at the end of the review will aid the surgeons in performing this technique to provide maximum benefit to patients suffering from the potentially blinding condition of LSCD.

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.

"Doughnut" Amniotic Membrane Transplantation With Penetrating Keratoplasty for Vernal Keratoconjunctivitis With Limbal Stem Cell Disease.

PURPOSE: Severe vernal keratoconjunctivitis (VKC) can cause ocular surface disease including partial or complete limbal stem cell deficiency (LSCD), especially in early-onset and severe limbal form of VKC. We report a novel technique of doughnut amniotic membrane transplantation (AMT) along with penetrating keratoplasty (PK) for management of partial LSCD and corneal scarring in a case of severe VKC. METHODS: Case report. RESULTS: A 17-year-old boy, with onset of disease at 8 years of age, and development of partial LSCD and corneal scarring over a period of 9 years despite therapy, presented with profound visual loss due to dense bilateral corneal scarring. After the active allergy subsided, he underwent modified AMT (doughnut AMT) with simultaneous PK in his left eye. Histopathology of the excised button revealed conjunctival phenotype and dense corneal scarring up to the posterior stroma. At 1-year follow up, his best spectacle-corrected visual acuity was maintained at 20/30 in the operated eye, the graft was clear, and the ocular surface was stable. CONCLUSIONS: Severe VKC can cause ocular surface disease including LSCD with corneal scarring, especially in early-onset limbal form of VKC. The modified technique of AMT (doughnut AMT) along with PK can successfully visually rehabilitate and address partial LSCD in such patients.

Lateral Rectus Muscle Injury During Double-Headed Pterygium Surgery: A Rare Complication.

A 43-year-old man developed double vision, esotropia, and abduction limitation after excision of a doubleheaded pterygium. Exploration during strabismus surgery 4 months later revealed a partially severed lateral rectus muscle and extensive conjunctival scarring. Direct injury to the lateral rectus muscle during pterygium surgery is extremely rare. Prevention and management strategies are discussed. [J Pediatr Ophthalmol Strabismus. 2020;57:e96-e99.].

Are high-efficiency particulate air (HEPA) filters and laminar air flow necessary in operating rooms to control acute post-operative endophthalmitis?

Purpose: To compare the five-year incidence of acute post-operative endophthalmitis following cataract surgery, between centers with and without laminar air flow and high-efficiency particulate air (HEPA) filters in operating rooms. Methods: Retrospective analysis of medical records of patients operated in a single network of a tertiary and four secondary hospitals across north India. Cases of endophthalmitis were identified from the records between January 2013 and June 2018. Protocols and consumables were standardized across all hospitals. The only infrastructural difference being the presence of laminar air flow and high energy particulate air filters in operating rooms of the tertiary center. The type of surgery, along with the demographic and socio-economic details, were captured and analyzed, using z-test for proportions and logistic regression. Results: Out of 88,297 cataract surgeries conducted, 36 cases of endophthalmitis were reported. The incidence of endophthalmitis across the network was estimated to be 0.041%, (95% CI: 0.027 to 0.054). There was no statistically significant difference between the incidence of POE at the tertiary (0.042%) and secondary centers (0.039%). Certain risk factors for high endophthalmitis incidence were identified, namely patients undergoing small incision cataract surgery and belonging to lower socio-economic status. However, for both factors the difference was not statistically significant. Conclusion: The five-year incidence of acute post-operative endophthalmitis in our network was found comparable to the best reported in literature. Incidence at secondary centers, without laminar air flow and high energy particulate air filters was found comparable to that in the tertiary center having these facilities.

Reappearance of limbal pigmentation post-simple limbal epithelial transplant.

We report the repigmentation at the limbus in patients who underwent simple limbal epithelial transplant (SLET) for uniocular chemical injury. The first case is of an 8-year-old child who presented with grade 4 chemical injury, with limbal stem cell deficiency (LSCD) corresponding to 6 o' clock till 11 o' clock. He was managed by amniotic membrane graft in the acute stage and SLET after 6 months of the initial injury. The second case is of a 15-year-old female who presented with lime injury, which had resulted in 6 o' clock of limbal involvement (10 o' clock till 4 o' clock). The patient was managed on similar lines with amniotic membrane graft (AMG) in the acute phase and SLET after 6 months of injury. The ocular surface was stable in both the patients post-SLET. The effected limbus showed pigmentation at 8 months of follow-up which eventually became distinct and remained stable. We speculate that the pigmentation at limbus could be attributed to proliferation and movement of melanocytes from limbal biopsy in SLET. These may be capable of supporting the proliferation of limbal epithelial cells and modulation of corneal wound healing.

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.