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To assess outcomes of limbal stem cell deficiency (LSCD) in patients treated with Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE).Retrospective case series. Patients with LSCD who received PROSE treatment were included. Data including best-corrected visual acuity (BCVA) and LSCD staging before and after PROSE dispensing were collected to characterize each case.Five eyes of four patients were included. All patients were female, with an age range of 21 to 80 years. Each patient received a PROSE device with diameters ranging from 16 to 18.5 mm. Follow-up ranged from 11 to 29 months. Tolerated wear times ranged from 3.5 to 10 hr daily. Four eyes showed improved BCVA and unchanged LSCD staging as per the global consensus after PROSE treatment. Three of these eyes had stage 3 and one had stage 1C LSCD at diagnosis. The fifth eye had worse BCVA and recurrence of stage 3 LSCD post-living-related conjunctival limbal allograft transplant despite PROSE treatment.Prosthetic Replacement of the Ocular Surface Ecosystem may be a viable treatment for LSCD, including severe cases, because it can provide symptom relief and improve vision. Its customizability, as demonstrated in this study, is beneficial for troubleshooting issues with fitting. Future studies are needed to further assess PROSE as treatment for LSCD.

Taking into consideration prior human experience with treating limbal stem cell deficiency (LSCD) with cultivated limbal epithelial cells (CLEC) from other countries, we have set a goal to optimize and standardize the techniques of CLEC preparation (called CALEC by our group) for the clinical trial in the United States.We performed an extensive literature review of all human trials, case series, and reports involving autologous cultivated limbal epithelial cell transplantation. Allogeneic cultivated limbal epithelial cell transplantations were reported only when combined with autologous studies. We also searched prior animal data aiding in detailing regulatory toxicology requirements.Between 1997 and 2020, the analysis of human trials revealed 21 studies on autologous grafts, and 13 studies analyzing both autologous grafts and allogeneic grafts. Of a total of 34 studies, 6 studies used good manufacturing process (GMP) facilities, and 11 studies had no animal-derived products or murine feeder layers, whereas only 1 study had both. Overall, the treatment with autologous CLEC grafts was 68.9% successful. In total there were 6 preclinical studies using rabbits, serving as surrogate studies to assess the safety and toxicity of cultivated limbal epithelial cells for human trials. Based on prior human experience, we further optimized the manufacturing conditions with GMP-grade and serum and animal-free reagents, and developed cell characterization assays for the CALEC product release.These data were used to develop a novel and consistent manufacturing process using only qualified and validated reagents for performing the first clinical trial on CALEC transplantation to treat LSCD in the United States.

To investigate if human oral mucosal fibroblasts (HOMF) from patients with limbal stem cell deficiency (LSCD) can be used as an autologous feeder layer to support the culture of epithelial cells for potential clinical use.HOMF were isolated from oral mucosal biopsies obtained from the following groups of patients with LSCD: aniridia, mucous membrane pemphigoid (MMP), Stevens-Johnson syndrome (SJS), and ectodermal dysplasia (ED). The ability of these cells to support the culture of human limbal epithelial cells (HLE) was compared to that of HOMF from non-LSCD donors and 3T3s commonly used to culture epithelial cells for use in the clinic to treat LSCD.HOMF were successfully obtained by explant culture for 3/3 aniridia patients, 3/3 MMP patients, 1/3 SJS patients, and 1/1 ED patients. All HOMF cultured from these LSCD groups supported the expansion of HLE with epithelial culture times and total colony forming efficiency (CFE) comparable to those achieved on HOMF isolated from donors without LSCD. PCR showed that all HLE cultured on LSCD donor HOMF expressed p63α, CK15, PAX6, CK12, and MUC16 as did HLE cultured on the control non-LSCD donor HOMF and 3T3s. Western blotting detected CK15 and MUC16 protein expression in all groups.HOMF from patients with LSCD can be successfully used to support the expansion of epithelial cells. These cells may therefore be useful as autologous feeder fibroblasts for the expansion of epithelial cells for use in the clinic to treat LSCD.

A 39-year-old man presented with both eyes limbal stem cell deficiency status post chemical injury. He was managed initially with topical medications to subside the ocular surface inflammation. Over the course of subsequent visits, the fibrovascular pannus over the cornea gradually progressed, leading to further diminution of vision in left eye more than right eye. Since, the ocular surface was wet, the patient committed for lifelong immunosuppression and his brother consented to donate healthy limbal tissue; he underwent living-related allogeneic simple limbal epithelial transplantation in the left eye.

The aim of this study was to investigate basal epithelial cell morphology (CM) in the central cornea and limbal areas of eyes with limbal stem cell deficiency (LSCD).This was a prospective, cross-sectional comparative study. We developed a CM scoring system based on basal epithelial cell phenotypes graded from 0 (normal) to 3 (severe morphologic alterations); this system was evaluated by 2 independent masked observers. The CM score was compared with the LSCD clinical score, mean best-corrected visual acuity, and in vivo laser scanning confocal microscopy parameters used to stage LSCD (ie, basal epithelial cell density, basal epithelial thickness, and subbasal corneal nerve fiber length density).One hundred sixty-eight eyes with LSCD and 63 normal eyes were included. Compared with the control group, the LSCD group had significantly higher mean (±SD) CM scores in the central cornea (1.8 ± 0.7 vs. 0.5 ± 0.4, respectively; P = 0.01) and limbal areas (1.6 ± 0.2 vs. 1.3 ± 0.0, respectively; P0.05). The mean CM score in the central cornea was positively correlated with the clinical score ( P0.01, r = 0.66) and negatively correlated with the best-corrected visual acuity ( P0.01, r = 0.42). The CM scores were positively correlated with all other in vivo laser scanning confocal microscopy parameters in the central cornea and limbal areas (all P0.001).Basal epithelial CM is altered in the central cornea and limbus of eyes with LSCD and thus can be used to stage the clinical severity of the disease.

We report the sensitivity and specificity of van Herick (VH) grading in detecting gonioscopically-defined primary angle closure suspects (PACS) among subjects screened for participation in a population-based trial in southern China. A cut-off of VH≤25% was found to have sensitivity and specificity rates of 98.2% and 25.9%, respectively. Rates were adjusted for missing gonioscopy data, resulting in a sensitivity and specificity of 92.5% and 61.5%, respectively.

BackgroundTopical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial wound healing.MethodsCorneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL β-blocker levobunolol, β1-adrenoceptor (β1AR)-specific antagonist atenolol or β2-adrenoceptor (β2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining.ResultsLevobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium.Conclusionβ-blocker eye drops impaired corneal wound healing by inhibiting the β2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective β1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.

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.

To investigate the etiology and long-term surgical prognosis of the abnormal epithelium for partial limbal stem cell deficiency (LSCD), following superficial keratectomy DESIGN: Retrospective, interventional case series METHODS: This single-center, retrospective study was conducted to assess the prognosis of consecutive patients who underwent superficial keratectomy, with or without amniotic membrane transplantation (AMT), for the treatment of partial LSCD, from 2010 to 2019. We analyzed the etiologies of partial LSCD, surgical success rate, prognosis for recurrent cases, and the improvement in visual acuity.We included 40 patients (51 eyes) with partial LSCD. All eyes were in clinical stage II without dense fibrovascular tissue. Idiopathy was the most common etiology (39%), followed by multiple surgeries involving the corneoscleral limbus (19%). All eyes attained corneal reepithelialization and transparency. Furthermore, the visual acuity improved or remained unchanged postoperatively. We observed recurrence in 19 eyes (37%) with a mean follow-up period of 26.3 months. Despite no significant difference in the recurrence rates among different etiologies, postoperative delayed epithelialization and extensive limbal involvement were identified as risk factors for recurrence (P.001 and P = .013, respectively). Repeat surgeries were performed in 16 eyes. The final success rate was 84%.Superficial keratectomy is useful for the treatment of partial LSCD of varied etiologies, with an expected improvement in visual acuity postoperatively. Although the procedure can be repeated and have a high success rate, there have been several cases of recurrence in the long-term postoperative course.

Purpose To investigate the safety and feasibility of topical injection of bone marrow derived mesenchymal stem cells (BM-MSCs) in acute severe ocular burns. Methods In this open-label，single-arm study, subconjunctival injection of allogenic BM-MSCs combined with standard treatment was given to 16 patients with acute severe ocular burns (Dua's grade IV to VI) within 2 weeks after injury. The primary outcome was efficacy rate which referred to the proportion of complete corneal epithelialization patients without perforation. The secondary outcome was safety, visual acuity, the number of symblephara, and elevated intraocular pressure. Results One patient was lost to follow-up. During the follow-up period, no corneal perforation was developed. Complete corneal epithelialization was noted 8 (ranged 4–10 weeks) weeks after treatment in 13 eyes (81.3%). The efficacy rate was 87.5% (95% confidence interval, CI: 61.7–98.4). Hypopyon was detected and later well controlled in 1 eye. Partial or total limbal stem cell deficiency (LSCD) was noted in all eyes. Improvement of visual acuity was achieved in 5 out of 16 eyes (31.3%). Seven eyes’ visual acuity was reached 0.1. Symblepharon with varied severity was noted in 5 eyes. Two eyes had elevated intraocular pressure. Conclusions This study confirms the safety of subconjunctival injection of BM-MSCs as an innovative and convenient procedure in ocular burns. The overall result is promising considering the absence of perforation, the low severity of symblepharon and visual acuity improvement.

To evaluate safety and efficacy of autologous serum eye drops (AS) in the treatment of limbal stem cell deficiency (LSCD) associated with glaucoma surgery.Retrospective case series of eyes with glaucoma surgery-induced LSCD treated with AS. Diagnosis of LSCD was confirmed by anterior segment optical coherence tomography, in vivo confocal microscopy, and/or impression cytology. Limbal stem cell deficiency severity was staged using a clinical scoring system (2-10 points). Outcome measures were changes (≥2 points) of the LSCD score and best-corrected visual acuity (BCVA) from the baseline to the last follow-up.Thirteen eyes of 12 consecutive patients treated with 50% AS for at least 3 months were included. The mean age was 78.9±7.5 years and the mean duration of AS use was 20.9±16.8 months. Indications of AS included LSCD progression in eight eyes (61.5%) and visual axis threatening in five eyes (38.5%). The mean LSCD score at baseline (6.7±1.6) was similar to that at last follow-up (6.5±2.2, P =0.625). Two eyes (15.4%) showed improvement, nine eyes (69.2%) were stable, and two eyes (15.4%) worsened. The mean baseline BCVA (0.89±0.64 logMAR) was similar to the mean final BCVA (1.05±0.63 logMAR, P =0.173). There were no serious adverse complications related to AS.AS appears to be well tolerated and may stabilize the progression of LSCD with limited effects. A larger study is necessary to confirm the findings.

Purpose How sensory neurons and epithelial cells interact with one another, and whether this association can be considered an indicator of health or disease is yet to be elucidated. Methods Herein, we used the cornea, Confetti mice, a novel image segmentation algorithm for intraepithelial corneal nerves which was compared to and validated against several other analytical platforms, and three mouse models to delineate this paradigm. For aging, eyes were collected from 2 to 52 week-old normal C57BL/6 mice (n ≥ 4/time-point). For wound-healing and limbal stem cell deficiency, 7 week-old mice received a limbal-sparing or limbal-to-limbal epithelial debridement to their right cornea, respectively. Eyes were collected 2–16 weeks post-injury (n=4/group/time-point), corneas procured, immunolabelled with βIII-tubulin, flat-mounted, imaged by scanning confocal microscopy and analyzed for nerve and epithelial-specific parameters. Results Our data indicate that nerve features are dynamic during aging and their curvilinear arrangement align with corneal epithelial migratory tracks. Moderate corneal injury prompted axonal regeneration and recovery of nerve fiber features. Limbal stem cell deficient corneas displayed abnormal nerve morphology, and fibers no longer aligned with corneal epithelial migratory tracks. Mechanistically, we discovered that nerve pattern restoration relies on the number and distribution of stromal-epithelial nerve penetration sites. Conclusions Microstructural changes to innervation may explain corneal complications related to aging and/or disease and facilitate development of new assays for diagnosis and/or classification of ocular and systemic diseases.

PURPOSE To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning. METHODS This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus. RESULTS A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position. CONCLUSION True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.

PURPOSE To describe the histopathological characteristics of limbal stem cell deficiency (LSCD) due to chronic vernal keratoconjunctivitis (VKC). METHODS This retrospective study included 14 eyes of 13 patients who underwent simple limbal epithelial transplantation for total LSCD from 2017 to 2018. The histological characteristics of the excised fibrovascular pannus were compared between 2 groups of 7 eyes, each with LSCD due to VKC and chemical burns (CB). Histological characteristics and type of inflammation were studied using special stains and immunohistochemistry. Fisher exact test was used to detect the statistical significance of the histological differences between both groups. RESULTS Epithelial hypertrophy, epithelial downgrowth, and eosinophilic infiltration were noted in all eyes in the VKC group (7/7, 100%). Epithelial hypertrophy was noted in 3 of the 7 (42.8%) eyes in the CB group, whereas epithelial downgrowth and eosinophilic infiltrates were absent. The average chronic inflammatory score of the pannus (5.28) was higher in VKC than in CB (3.85; P = 0.1080). The presence of goblet cells was higher in the CB group (5/7, 1.4%) than in the VKC group (3/4, 2.8%), although not statistically significant. Other histological differences between the groups were not statistically significant. CONCLUSIONS The histopathological features of LSCD in VKC reveal some distinctive characteristics. These include the presence of epithelial downgrowth, eosinophilic infiltration, and epithelial solid and cystic implants. Although this information may be used to establish the diagnostic criteria for VKC as the cause of LSCD, further studies are needed to elucidate the reasons behind these unique findings.

The purpose of this study was to report a case of "smoldering" keratolimbal allograft (KLAL) rejection in a patient with subtherapeutic levels of systemic immunosuppression in temporal association with BNT162b2 messenger RNA vaccination for severe acute respiratory syndrome coronavirus 2.This was a case report.A 72-year-old man presented with circumferential perilimbal engorgement, stagnation, and tortuosity of vessels with mild chemosis in his right eye KLAL segments 1 month after receiving the BNT162b2 messenger RNA vaccine while his tacrolimus trough blood levels were subtherapeutic measuring2 ng/mL. He had undergone KLAL 6.5 years before for total limbal stem cell deficiency from a chemical injury and had been stable without any history of rejection. The donor was blood type O, and the patient had no systemic comorbidities. The patient was treated with hourly difluprednate 0.05% and increasing of his oral tacrolimus dose to 2 mg twice a day with improvement of rejection signs.There may be a temporal association between KLAL rejection after immunization against severe acute respiratory syndrome coronavirus 2 in patients with subtherapeutic levels of systemic immunosuppression. Patients should be on alert for any ocular signs or symptoms postimmunization and present for treatment immediately.

Purpose: To assess the efficacy and safety of human leukocyte antigen-matched allogeneic cultivated limbal epithelial stem cell grafts in the treatment of aniridia-associated keratopathy (AAK). Methods: Six eyes of 6 patients with severe AAK received an allogeneic stem cell graft between January 2010 and March 2017. Anatomical and functional results were assessed at 6 months, 1 year, 2 years, and the final follow-up visit available. Safety analysis was performed by considering all perioperative and postoperative adverse events and additional surgeries required during the follow-up period. Results: The mean follow-up was 53.6 months (range 24-104 months). In most patients (80%), there was an early improvement of the keratopathy postoperatively, which slowly regressed during longer follow-up. At the final follow-up, 4 of the eyes were graded as failure and 1 eye was graded as partial success. Grading the sixth eye was not possible because of an adverse event. None of the patients maintained a total anatomical success in the long-term. Only 1 patient maintained a modest improvement in best-corrected visual acuity from hand motion to counting fingers. Four serious adverse events were recorded in 2 patients. Conclusions: Severe AAK remains a challenging condition to manage. Transplantation of allogenic ex vivo cultivated limbal stem cells may provide a temporary improvement in ocular surface stability, but anatomical and functional results are poor in the long-term. The eyes are prone to adverse events, and any surgical treatment should take this into consideration.

To elucidate the microarchitecture of limbus and cornea in subjects with Vogt Koyanagi Haradas syndrome (VKH).From January 2019 to December 2019 a total of 17 VKH subjects, 5 acute and 12 chronic, 18 non VKH uveitis controls, and 6 healthy controls were recruited for this study . In vivo confocal microscopic (IVCM) analysis of the limbal basal epithelium, scleral side of the limbus, limbal niche, corneal keratocytes, and corneal nerves was carried out .Absence of pigmented cells in the limbal basal epithelium, presence of inflammatory cells on the scleral side of the limbus, fibrotic niche, degenerated keratocytes, thinning, and beading of corneal nerves were noted in VKH eyes as compared to controls.Presence of inflammatory cells and depigmentation of limbus in chronic VHK points to disease progression.Keratocyte and corneal nerve changes in Vogt Koyanagi Haradas syndrom are novel findings.

Purpose This systematic review (SR) assessed the efficacy, safety and cost-effectiveness of cell-based therapy to manage limbal stem cell deficiency (LSCD), a sight-threatening orphan condition most frequently associated with severe chemical or thermal burns. LSCD has historically been treated by transplanting limbal tissue. In 1997, a new treatment, cultured limbal epithelial autografts, was described for unilateral LSCD. In cases of bilateral disease cultured autologous oral mucosa stem cells have been used. The relative efficacy of different cultured tissue procedures is unknown. Methods A protocol was registered with PROSPERO (CRD42017081117). Searches were conducted in 14 databases and 6 conference websites. Two reviewers independently selected studies, conducted data extraction and assessed risk of bias. One reviewer extracted individual patient data (IPD); a second checked extracted data. Data were assessed to determine the feasibility of statistical analysis, with Bayesian synthesis used to estimate improvement achieved by different treatments. Results Fifty-two studies were eligible for inclusion (1113 eyes); 41 studies (716 eyes) reported IPD. No evidence was identified on cost-effectiveness. This SR was unable to confirm that any of the types of ex vivo cultured stem cell transplants identified for LSCD treatment were statistically superior when assessed against the outcomes of interest. Conclusions We believe this SR is the first to include IPD analysis of LSCD data. There is no evidence for the superiority of any method of limbal stem cell transplant. Confirmation of the safety and efficacy of this treatment modality is challenging due to heterogeneity within and between the studies identified. Therefore, recommendations for future research are proposed.

To investigate the corneal epithelial and limbal epithelial alterations in patients under topical glaucoma treatment using anterior segment-OCT (AS-OCT) and to determine the changes of the limbal region due to the preservatives and glaucoma drugs, that can progress to limbal stem cell deficiency (LSCD). Limbal thickness was measured by AS-OCT to evaluate limbal cell deficiency.Forty-seven patients using topical medication for glaucoma, and 48 control subjects were enrolled in this matched case-control study. The patients were divided into four groups according to the treatment regimens. Group 1: One-drug regimen, Group 2: Two-drug regimen, Group 3: Three-drug regimen, Group 4: Four-drug regimen For the ocular surface evaluation; tear break-up time with standard fluorescein sodium sterile strip application, Schirmer test-I, Ocular Surface Disease Index Questionnaire, and AS-OCT were performed.A total of 95 subjects were included: 47 eyes of 47 patients with glaucoma medication and 48 eyes of 48 healthy subjects. There was a statistically significant difference between patients and controls according to BUT, SCH, and OSDI (Using at least one glaucoma drug caused limbal area injury, changed ocular surface measurements, and significantly reduced the limbal epithelial thickness where the stem cells reside. The limbal epithelial thickness measurement by AS-OCT seems to be an innovative, non-invasive, and promising technique for detecting and staging corneal damage in topical glaucoma therapy.

Aim: Chemical injuries can potentially lead to the necrosis anterior segment of the eye, and cornea in particular. Inflammatory cytokines are the first factors produced after chemical ocular injuries. Inflammation via promoting the angiogenesis factor tries to implement the wound healing mechanism in the epithelial and stromal layer of the cornea. Methods: Narrative review.Results: In our review, we described the patterns of chemical injuries in the cornea and their molecular mechanisms associated with the expression of inflammatory cytokines. Moreover, the effects of inflammation signals on angiogenesis factors and CNV were explained. Conclusion: The contribution of inflammation and angiogenesis causes de novo formation of blood vessels that is known as the corneal neovascularization (CNV). The new vascularity interrupts cornea clarity and visual acuity. Inflammation also depleted the Limbal stem cells (LSCs) in the limbus causing the failure of normal corneal epithelial healing and conjunctivalization of the cornea.

AimsTo report the global uptake of simple limbal epithelial transplantation (SLET) and compare the economic, clinical and social outcomes of SLET with those of cultured limbal epithelial transplantation (CLET).MethodsA comprehensive literature review and an online survey of eye surgeons were conducted to understand the efficacy and current uptake of SLET surgery. A de novo economic model was developed to estimate the cost savings with SLET compared with CLET. Our economic analysis is conducted from an Indian perspective, as this is where the technique originated. A scenario analysis using the UK cost data and a user-friendly Excel model is included to allow users to input the costs from their setting to estimate the cost savings with using SLET compared with using CLETResultsThe anatomical success with SLET in adults (72.6% (range 62%–80%)) was the same as CLET (70.4% (range 68%–80.9%)). For children, the outcome for SLET (77.8% (range 73%–83%)) was better than with CLET (44.5% (range 43%–45%)). In response to our informal questionnaire, 99 surgeons reported to have performed SLET on 1174 patients in total. They appreciated that SLET negates the requirement for costly tissue engineering facilities. Results of economic analysis suggested that SLET provided an estimated cost-savings of US$6470.88 for adults and US$6673.10 for children. In broad terms, the cost of SLET is approximately 10% of the cost of CLET for adults and 8% for children.ConclusionSLET offers a more accessible and financially attractive alternative to CLET to treat limbal stem cell deficiency.

Aim To report the preliminary outcomes and elucidate the possible rationale of alloSLET for primary ocular surface reconstruction following excision of extensive ocular surface tumors. Methods Retrospective interventional case series with a minimum postoperative follow up of 1 year. AlloSLET was performed along with wide surgical excision and cryotherapy in 3 eyes. Results Of the 2 eyes with extensive OSSN and one with an extensive pigmented lesion, there was no occurrence of symblepharon in all 3 eyes. No features suggestive of LSCD was noted in 2 eyes. In the child with xeroderma pigmentosum and OSSN, early peripheral vascularization was noted at 1 year of follow up with reduced vision secondary to amblyopia. Conclusion Primary alloSLET could be an alternative to primary autoSLET in eyes with extensive ocular surface tumors, commonly seen with ocular surface squamous neoplasia (OSSN) and pigmented lesions. This facilitates ocular surface reconstruction with reduced occurrence of symblepharon formation as well as limbal stem cell deficie4ncy (LSCD). It possibly, is the only option in eyes with OSSN with coexistent bilateral limbal insufficiency. It may obviate the need for autoSLET, primary or secondary in eyes with adequate residual limbus.

PURPOSE OF REVIEW The aim of this study was to provide a comprehensive summary of in-vivo imaging techniques of the aqueous outflow system and discuss its role in improving our understanding of glaucoma pathogenesis and management. RECENT FINDINGS Our understanding of the aqueous outflow system is largely derived from ex-vivo studies. Recent innovations in imaging technology and techniques enable in-vivo evaluation of the conventional outflow system in real-time. Optical coherence tomography allows for noninvasive, high-resolution, volumetric imaging of ocular tissues. Dynamic structural changes have been observed at the trabecular meshwork and Schlemm's canal. In parallel, aqueous angiography using injected tracers show a similar dynamism with variable and pulsatile flow signals. SUMMARY In-vivo imaging enable real-time evaluation of the conventional aqueous outflow pathway. This emerging field shows great promise to expand our understanding of the pathogenesis and treatment of glaucoma.

To conduct a systematic review of clinical research on the use of regenerative medicine for the cornea in human patients. A systematic literature search of MEDLINE and the Cochrane Library was performed in May 2020. Forty-two articles were identified. Thirty-eight of those articles focused on the treatment for limbal stem cell deficiency (LSCD), of which 17 articles involved autologous cultured limbal epithelial cell sheet transplantation (CLET), 13 involved allogeneic CLET, and 14 involved autologous cultured oral mucosal epithelial cell sheet transplantation (COMET). For autologous CLET, the median ocular surface reconstruction rate, visual recovery rate, incidence of immunologic rejection, infectious keratitis, and ocular hypertension/glaucoma were 74.1%, 54.5%, 0%, 4.6%, and 6.3%, respectively. For allogeneic CLET, they were 71.4%, 71.4%, 7.1%, 12.0%, and 7.1%, respectively. For autologous COMET, they were 66.7%, 66.7%, 0%, 5.3%, and 8.1%, respectively. Systemic immunosuppressants and steroid medications were predominantly used following allogeneic CLET, whereas they were not routinely used after autologous CLET. Three studies focused on the treatment of keratoconus using autologous adipose-derived adult stem cells and reported no marked adverse events. One study reported on the treatment of bullous keratopathy using allogeneic cultured corneal endothelial cells. All patients achieved an endothelial cell density of >500 cells, and the corrected distance visual acuity improved in 82% of the treated eyes. The results show that regenerative medicine for the cornea demonstrated a satisfactory efficacy and safety. Through translational research, we are expecting to establish a new treatment for waiting patients.

Significance This study evaluates the reliability and validity of an automatic method of the external and internal limbal points identification from anterior segment optical coherence tomography (OCT) images in comparison with manual delineation. Purpose The purpose of this work was to evaluate the repeatability and precision of a previously proposed automatic method of external and internal limbal points identification and to compare them with the manual delineation by experienced clinicians in terms of limbus diameter. Methods Optical coherence tomography tomograms obtained for 12 healthy volunteers without a history of eye diseases were analyzed. Fifteen OCT tomograms were captured for each patient. For all the images, the external and internal limbal points were determined using both the automatic and manual methods. The external and internal limbus diameters were used as the comparative parameter between the methods under consideration. The statistical analysis included mean, standard deviation, the Passing-Bablok regression, and the Pearson correlation coefficient. Results A strong linear dependence between the automatic and manual methods was identified. While compared with the subjective estimates from clinicians, the automatic technique overestimated the external limbus diameter (bias equals 0.21 mm for optometrist and 0.23 mm for ophthalmologist) and slightly underestimated the internal limbus diameter (bias equals 0.13 mm for optometrist and 0.04 mm for ophthalmologist). The automatic method showed significantly better repeatability than the manual method in the case of external limbal points identification and comparably high repeatability for internal limbal points recognition. Conclusions Because of high precision and excellent repeatability, the automatic method of limbal points identification may be successfully used for estimation of the dynamic changes in the geometry of the anterior segment of the eye, where the large number of captured OCT images needs to be processed automatically with high precision.

Significance Cytokine and protease analysis revealed relative changes in the post-lens tear film of scleral lenses with low and high limbal clearances. Results from this study indicate that midperipheral lens fit is an important fitting feature that can impact the inflammatory response of a keratoconic eye. Purpose The purpose of this study was to investigate changes in levels of inflammatory mediators in the post-lens tear film of keratoconic scleral lens wearers with varying limbal clearance designs. Methods Twenty-two keratoconic eyes were fitted with two sets of scleral lenses that were consistent in lens diameter and central sagittal depth but varied in limbal clearance by approximately 50 μm. Lenses were worn in a randomly assigned order for a 2-week period each. At each follow-up visit, immediately after lens removal, tear samples were collected with a microcapillary tube (10 μL, 0.5 mm in diameter) from the bowl of the inverted scleral lens. Tear cytokine and protease analysis was performed using a multiplex electrochemiluminescent array (Meso Scale Discovery, Rockville, MD) instrument. Levels of interleukins 1, 6, and 8; tumor necrosis factor α; and matrix metalloproteinases 1 and 9 were compared and analyzed. Results Levels of interleukin 1β, tumor necrosis factor α, and matrix metalloproteinase 1 increased with high limbal clearance (P = .01, .006, and .02, respectively). No change in interleukins 6 and 8 levels was found (P > .05). A decrease in matrix metalloproteinase 9 was noted in post-lens tear film of scleral lenses with high limbal clearance (P = .10). Discussion Relative changes in the cytokine and protease levels were found when comparing low and high limbal clearance, indicating that the midperipheral lens fit is an important feature that can impact the inflammatory response of the keratoconic eye.

Background: To understand the pathogenesis of a central corneal dermoid (CD) in a 12-day-old child, a comparison of CD specimen was done with limbal dermoid (LD) and cadaveric corneal (CC) specimens by immuno-histochemical staining. Methods: The child underwent penetrating keratoplasty for visual rehabilitation. The corneal tissue was sent for histo-pathological and immunochemistry evaluation. The corneal specimen obtained was compared the origin of central CD with LD and CC based on their antigenic expression profile. Results: Clinically over a period of 75 months post operatively the child maintained a clear graft. Hematoxylin and Eosin staining of LD had a typical morphology including stratified keratinized epithelium, hair shaft with pilo sebaceous glands, eccrine sweat glands, lymphocytes, and blood vessels. Immuno-histochemical staining showed positive stain for Cytokeratin 3 epithelial marker in the epithelium of CC, LD, and CD. Smooth muscle maker (SMA) was identified in LD and CD but not in the CC as it is devoid of blood vessels. Limbal stem cell maker (P63) was detected only in LD. Vimentin, a mesenchymal stem cell marker stained positively in all three tissues of CC, LD, and CD. Conclusions: Corneal dermoid showed positive staining for mesodermal tissue components compared to both ectodermal and mesodermal components in limbal dermoid suggesting possibly a different origin of corneal dermoid

Purpose: To evaluate the accuracy of anterior segment optical coherence tomography (AS-OCT) for locating horizontal extraocular muscle (EOM) insertion after strabismus surgery. Methods: The distance from the limbus to the postoperative muscle insertion was measured with calipers intraoperatively and by AS-OCT during the postoperative visit of adults undergoing strabismus surgery. Images were collected by masked technicians. Intraclass correlation coefficients (ICC) were used to evaluate the agreement between measurements. Results: Twenty-eight patients were recruited. Measurements were taken from 31 eyes, including 17 lateral and 14 medial rectus muscles. EOM insertion was successfully identified by AS-OCT for 14 (45%) cases. The ICC between intra-operative and AS-OCT measurement was 0.886 when the distance from the limbus to the insertion of EOM was less than 8 mm and 0.001 when the distance from the limbus was between 8 and 10 mm. EOM insertion was undetectable if distance to the limbus was greater than 10 mm. Conclusions: AS-OCT can accurately identify post-surgical horizontal muscle insertion if the insertion is less than 8 mm from the limbus. [ J Pediatr Ophthalmol Strabismus . 2021;58(1):62–65.]

We investigated the effects of different intraoperative eyeball fixation techniques (superior rectus muscle suture [MS] and traction suture at the corneal limbus [CS]), on intraocular pressure (IOP) and the incidence of ptosis after phacotrabeculectomy. Forty-one eyes with different glaucoma types which qualified for phacotrabeculectomy were included. Twenty-three and eighteen patients were included in the CS and MS groups, respectively. The IOP, best-corrected visual acuity (BCVA), and margin reflex distance were assessed preoperatively and 3, 6, and 12 months post-operatively. Preoperatively, the mean IOPs (± standard deviation) in the CS and MS groups were 23.6 ± 7.3 mmHg and 24.3 ± 6.6 mmHg (p > 0.05), respectively. At 3 and 6 months post-surgery, the mean IOPs were significantly lower in the CS group than in the MS group: 13.9 ± 3.0 mmHg vs. 17.7 ± 3.5 mmHg (p = 0.001), and 13.9 ± 4.9 mmHg vs. 17.2 ± 3.5 mmHg (p = 0.005), respectively (mean difference: 3.9, 95% confidence interval 1.7–6.1). At 12 months, the mean postoperative IOPs were 15.2 ± 3.5 mmHg and 14.9 ± 3.6 mmHg in the CS and MS groups, respectively (p > 0.05). At 6 months, the BCVAs were 0.91 ± 0.15 and 0.71 ± 0.3 (p = 0.029) in the CS and MS groups, respectively; BCVAs were 0.91 ± 0.15 and 0.71 ± 0.3 (p = 0.029) in the CS and MS groups, respectively; the difference was non-significant 12 months post-surgery (0.78 ± 0.32 vs. 0.74 ± 0.30, p = 0.553). Postoperative ptosis was observed in 4 (17%) and zero patients in the CS and MS groups, respectively, but the difference was not statistically significant (p = 0.118). The study was not powered sufficiently to detect statistically significant changes in exploratory endpoints. The study was not powered sufficiently to detect statistically significant differences between groups in exploratory endpoints.

AimTo compare the immunocytochemistry (ICC) on impression cytology of corneal surface epithelium after simple limbal epithelial transplantation (SLET) and conjunctival-limbal autograft (CLAU).MethodsA prospective study of 20 patients above 1 year of age with chronic chemical burns, who underwent limbal stem cell transplantation (LSCT). They were divided equally in group A (SLET) and group B (CLAU). ICC was done for cytokeratin 3 (CK3) and cytokeratin 19 (CK19), preoperatively and postoperatively at 6 months.ResultsFour cases were excluded due to inadequate cellularity in preoperative or postoperative samples. On ICC analysis, in the remaining 16 patients mean CK3 and CK19 positivity changed from 2.06%±1.73% and 83.56%±8.69% preoperatively to 70.62%±13.2% (pThree patients with complete reversion had clear corneas at 6 months.ConclusionReversion of the epithelium to corneal phenotype was documented post LSCT with no difference in expression of CK3 between the two procedures (SLET/CLAU).

In this article, we introduce a modified technique of minor ipsilateral simple limbal epithelial transplantation (mini-SLET) in pediatric patients of limbal stem cell deficiency (LSCD). Two children with unilateral partial LSCD underwent the innovative technique of mini-SLET, where harvested limbal tissues were placed over the raw cornea and were covered with amniotic membrane. Both patients were followed till 9 months. Both cases showed favorable outcome and uneventful recovery. Results were comparable with the classical technique. This innovative modification of mini-SLET is safe, feasible, and an effective alternative with favorable visual outcome especially in pediatric population. It can be a breakthrough for LSCD management in developing countries with limited resources.

The chronic sequelae of Stevens-Johnson syndrome cause severe ocular morbidity. Among the various manifestations, including dry eye, cicatrization causing forniceal shortening, adnexal disorders, lid margin keratinization, and limbal stem cell deficiency, keratinization of the lid margin leads to progressive ocular surface damage through constant blink-induced microtrauma. This damage induces corneal punctate keratopathy and neovascularization and can produce epithelial defects leading to corneal infection or perforation. Management strategies for chronic ocular sequelae are broadly categorized into ocular surface stabilization procedures, tectonic procedures, and visual rehabilitation procedures. Interventions in the acute stage of the disease include amniotic membrane grafting. Timely intervention helps to prevent deterioration of the ocular surface in these eyes.

PURPOSE Panel-reactive antibody (PRA) testing has been widely adopted in solid organ transplantation for risk assessment in potential allograft recipients but has not been studied in the context of ophthalmic transplantation. The purpose of this study is to evaluate outcomes in patients undergoing ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) relative to preoperative PRA level. METHODS This is retrospective chart review of all eyes with documented PRA level that underwent OSST for LSCD between May 2000 and March 2019 at a single institution. Eyes with stable ocular surface but

Purpose To construct tissue engineered corneal epithelium from a clinical-grade human embryonic stem cells (hESCs) and investigate the dynamic gene profile and phenotypic transition in the process of differentiation. Methods A stepwise protocol was applied to induce differentiation of clinical-grade hESCs Q-CTS-hESC-1 and construct tissue engineered corneal epithelium. Single cell RNA sequencing (scRNA-seq) analysis was performed to monitor gene expression and phenotypic changes at different differentiation stages. Immunostaining, real-time quantitative PCR and Western blot analysis were conducted to detect gene and protein expressions. After subcutaneous transplantation into nude mice to test the biosafety, the epithelial construct was transplanted in a rabbit corneal limbal stem cell deficiency (LSCD) model and followed up for eight weeks. Results The hESCs were successfully induced into epithelial cells. scRNA-seq analysis revealed upregulation of ocular surface epithelial cell lineage related genes such as TP63, Pax6, KRT14, and activation of Wnt, Notch, Hippo, and Hedgehog signaling pathways during the differentiation process. Tissue engineered epithelial cell sheet derived from hESCs showed stratified structure and normal corneal epithelial phenotype with presence of clonogenic progenitor cells. Eight weeks after grafting the cell sheet onto the ocular surface of LSCD rabbit model, a full-thickness continuous corneal epithelium developed to fully cover the damaged areas with normal limbal and corneal epithelial phenotype. Conclusion The tissue engineered corneal epithelium generated from a clinical-grade hESCs may be feasible in the treatment of limbal stem cell deficiency.

Purpose This study was conducted to determine the long-term outcomes of cultivated cell sheet transplantation (CCST), and to clarify risk factors that affected the outcomes. Methods We retrospectively analyzed the medical charts and photographs of 246 consecutive surgeries (162 eyes from 139 patients) that used CCST for treating total limbal stem cell deficiency. Deficiency types included Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (SJS/TEN; n = 80), ocular surface burns (Burn; n = 75), ocular cicatricial pemphigoid (OCP) or pseudo-OCP (n = 58), and others (n = 33). The methods of CCST included 103 cultivated limbal epithelial transplantations (28 autologous, 62 allogeneic, and 13 living-related relatives), and 143 cultivated oral mucosal epithelial transplantations. We analyzed the rate of successful ocular surface reconstruction, clear corneas, and best-corrected visual acuity equal to or better than 20/200. Results With a mean observation period of 357 weeks, successful ocular surface reconstruction and clear corneas at last visit were achieved in 65.1% of the patients. Corrected visual acuity equal to or better than 20/200 was achieved in 19.0% of the patients. Eyes with SJS/TEN exhibited worse outcomes compared with the Burn group. Postoperative complications included corneal ulcerations or perforations (18.3%), glaucoma (13.8%), and infections (8.5%). Multivariate analyses using the logistic mixed-effects model indicated that the presence of preoperative corneal epithelial defects was a significant risk factor for postoperative failure. Conclusions In this series, the success rate of CCST after a mean observation period of 357 weeks was 65.1%, and preoperative epithelial defect was the most relevant risk factor.

PReCIS:: Regardless of the blood-filling patterns in Schlemm canal (SC) before the trabecular meshwork (TM) ablation, the trabectome surgery, combined with phacoemulsification, is effective for mild to moderate primary open-angle glaucoma patients. Purpose The purpose of this study was to evaluate the association between trabectome surgery outcomes and the blood filling patterns in SC before TM ablation. Materials and methods This retrospective cohort study included 105 eyes of 84 Japanese primary open-angle glaucoma patients who had undergone trabectome surgery in combination with cataract surgery. Provocative gonioscopy was performed before TM ablation to classify the blood filling patterns in SC into 3 groups: no filling (group 1); patchy/irregular filling (group 2); and complete filling (group 3). The subjects were divided into 3 groups according to the blood filling patterns and the trabectome surgery outcomes were compared, including intraocular pressure (IOP), the percentage reduction in IOP, surgical success rate, and the number of glaucoma medications. Success was defined by IOP ≤15 mm Hg and a >20% reduction in IOP with/without glaucoma medication, and without additional glaucoma surgery after trabectome surgery combined with cataract surgery. Results Twenty-four eyes were assigned to group 1, 48 to group 2, and 33 to group 3. Between-group analyses showed no significant intergroup differences in age (P=0.213), preoperative mean deviation (P=0.505), preoperative and postoperative IOP (P=0.941 and 0.458, respectively), preoperative and postoperative number of glaucoma medications (P=0.805 and 0.077, respectively), percentage IOP reduction (P=0.256), and success rates (P=0.540). Conclusion Trabectome surgery is effective for mild to moderate primary open-angle glaucoma patients, independent of the blood-filling patterns in SC before the TM ablation.

Purpose To evaluate the reliability of manual annotation when quantifying cornea anatomical and microbial keratitis (MK) morphological features on slit-lamp photography (SLP) images. Methods Prospectively enrolled patients with MK underwent SLP at initial encounter at 2 academic eye hospitals. Patients who presented with an epithelial defect (ED) were eligible for analysis. Features, which included ED, corneal limbus (L), pupil (P), stromal infiltrate (SI), white blood cell (WBC) infiltration at the SI edge, and hypopyon (H), were annotated independently by 2 physicians on SLP images. Intraclass correlation coefficients (ICCs) were applied for reliability assessment; dice similarity coefficients (DSCs) were used to investigate the area overlap between readers. Results Seventy-five MK patients with an ED received SLP. DSCs indicate good to fair annotation overlap between graders (L = 0.97, P = 0.80, ED = 0.94, SI = 0.82, H = 0.82, WBC = 0.83) and between repeat annotations by the same grader (L = 0.97, P = 0.81, ED = 0.94, SI = 0.85, H = 0.84, WBC = 0.82). ICC scores showed good intergrader (L = 0.98, P = 0.78, ED = 1.00, SI = 0.67, H = 0.97, WBC = 0.86) and intragrader (L = 0.99, P = 0.92, ED = 0.99, SI = 0.94, H = 0.99, WBC = 0.92) reliabilities. When reliability statistics were recalculated for annotated SI area in the subset of cases where both graders agreed WBC infiltration was present/absent, intergrader ICC improved to 0.91 and DSC improved to 0.86 and intragrader ICC remained the same, whereas DSC improved to 0.87. Conclusions Manual annotation indicates usefulness of area quantification in the evaluation of MK. However, variability is intrinsic to the task. Thus, there is a need for optimization of annotation protocols. Future directions may include using multiple annotators per image or automated annotation software.

ObjectiveUsing anterior segment optical coherence tomography (AS-OCT), we investigated the epithelial thickness (ET) of the central cornea and limbal regions in patients with limbal stem cell deficiency (LSCD) as a diagnostic and staging parameter.DesignProspective, cross-sectional study.MethodsThe central corneal epithelium thickness (CET) and maximum limbal epithelium thickness (mLET) were measured in the superior, inferior, nasal, and temporal limbus on AS-OCT images of the normal and eyes with LSCD. CET was obtained by 1-point (OCT-CET1) and 3-point measurement (OCT-CET3). The values of OCT-CET1 and OCT-CET3 were compared to the CET obtained with invivo confocal microscopy (IVCM-CET).ResultsSixty-eight eyes of 50 patients with LSCD and 52 eyes of 34 normal subjects were included. The mean (±standard deviation) OCT-CET3 was 55.0 ± 3.0μm (range, 50.6-62.0μm) in the control group and 41.6 ± 10.8μm (range, 0-56.3μm) in the LSCD group (P < .001). OCT-CET3 had a better correlation with IVCM-CET (r= 0.91) than did OCT-CET1 (r= 0.87, P= .001). The degree of reduction in OCT-CET3 increased in more advanced clinical stages of LSCD (all P < .001). The OCT-CET3 cutoff value that suggests LSCD was 46.6μm. Compared with the control group, the LSCD group had decreases in mLET in all 4 limbal regions (all P < .001). The sensitivity and specificity of OCT-CET3 is the highest among all mLET in detecting LSCD.ConclusionsBoth CET and mLET were thinner in patients with LSCD than in normal subjects. OCT-CET3 appears to be a reliable parameter to confirm LSCD when there is clinical suspicion.

To discuss and evaluate new technologies for a better diagnosis of corneal diseases and limbal stem cell deficiency, the outcomes of a consensus process within the European Vision Institute (and of a workshop at the University of Cologne) are outlined. Various technologies are presented and analyzed for their potential clinical use also in defining new end points in clinical trials. The disease areas which are discussed comprise dry eye and ocular surface inflammation, imaging, and corneal neovascularization and corneal grafting/stem cell and cell transplantation. The unmet needs in the abovementioned disease areas are discussed, and realistically achievable new technologies for better diagnosis and use in clinical trials are outlined. To sum up, it can be said that there are several new technologies that can improve current diagnostics in the field of ophthalmology in the near future and will have impact on clinical trial end point design.

Purpose In recent decades, the medical and surgical treatment of limbal stem cell deficiency (LSCD) has evolved significantly through the incorporation of innovative pharmacological strategies, surgical techniques, bioengineering, and cell therapy. With such a wide variety of options, there is a need to establish a global consensus on the preferred approaches for the medical and surgical treatment of LSCD. Methods An international LSCD Working Group was established by the Cornea Society in 2012 and divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to reach agreement on a strategic plan and methods after a comprehensive literature search. A writing group drafted the current study. Results A consensus in the medical and surgical management of LSCD was reached by the Working Group. Optimization of the ocular surface by eyelid and conjunctival reconstruction, antiinflammatory therapy, dry eye and meibomian gland dysfunction treatment, minimization of ocular surface toxicity from medications, topical medications that promote epithelialization, and use of a scleral lens is considered essential before surgical treatment of LSCD. Depending on the laterality, cause, and stage of LSCD, surgical strategies including conjunctival epitheliectomy, amniotic membrane transplantation, transplantation of limbal stem cells using different techniques and sources (allogeneic vs. autologous vs. ex vivo-cultivated), transplantation of oral mucosal epithelium, and keratoprosthesis can be performed as treatment. A stepwise flowchart for use in treatment decision-making was established. Conclusions This global consensus provides an up-to-date and comprehensive framework for the management of LSCD.

Significance Cyclodialysis clefts can potentially develop secondary to open globe injury. The swept-source anterior segment optical coherence tomography (SS-AS-OCT) may be a valuable diagnostic tool for the identification and estimation of the circumferential extent of cyclodialysis clefts. It could be considered an alternative when ultrasound biomicroscopy cannot be performed successfully. Purpose The purpose of this study was to report a case of open-globe injury associated with cyclodialysis cleft and the utility of SS-AS-OCT in its diagnosis. Case report A 12-year-old boy presented to the clinic because of penetrating ocular trauma to his left eye with a projectile stone. He was diagnosed with limbal perforation with uveal tissue prolapse and cataract. He underwent limbal repair with cataract extraction and posterior chamber intraocular lens implantation. However, even at the 6 weeks' post-operative period, he did not gain vision and had persistent hypotony with hypotonic maculopathy. Gonioscopy showed a 2-clock-hour superonasal cyclodialysis cleft. However, on SS-AS-OCT, it was discovered that the cleft extended along 5 clock hours, involving both superonasal and inferonasal quadrants. Recognizing the large extent of the cleft, endocyclopexy by modified sewing-machine technique was planned and performed. An IOP spike and improvement in vision were noted on the next post-operative day. The SS-AS-OCT confirmed cleft closure. Conclusions Although rare, cyclodialysis can occur in cases of open globe injury. The SS-AS-OCT is a useful diagnostic tool to study the circumferential extent of cyclodialysis and may unravel detachments hidden behind intact anterior ciliary body face.

1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma.A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency.Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities.New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.

PURPOSE To describe the presentation and management of limbal stem cell dysfunction in ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome. METHODS A retrospective case report. RESULTS A 6-day-old male infant was diagnosed with IFAP syndrome based on family history and a mutation detected in the MBTPS2 gene. Initial examination showed hyperkeratotic eyelids, madarosis, and lagophthalmos, but otherwise clear corneas. He developed bilateral central corneal epithelial defects spontaneously 6 months later, which were managed with aggressive lubrication, prophylactic antibiotics, and bilateral permanent lateral tarsorrhaphies at 7 months of age. During the procedure, the patient was noted to have bilateral limbal thickening, peripheral corneal pannus with underlying stromal scarring, and late fluorescein staining of the corneal surface. Anterior segment optical coherence tomography demonstrated a significantly abnormal and hyperreflective epithelial surface overlying a thinned corneal stroma, suggestive of limbal stem cell dysfunction. The corneal surface was maintained with lubrication and tarsorrhaphy and has remained stable since. CONCLUSIONS The progressive conjunctivalization, spontaneous epithelial defects, and anterior segment optical coherence tomography features are highly suggestive of limbal stem cell dysfunction in IFAP syndrome. Optimizing the ocular surface is of importance in the management of children with this rare disease.

OBJECTIVES: The conditioned-medium derived from corneal mesenchymal stromal cells (cMSCs) has been shown to have wound healing and immunomodulatory effects in corneal injury models. Here, the therapeutic effects of lyophilized cMSC conditioned-medium were compared with fresh conditioned-medium. METHODS: The epithelial wound healing effects of fresh and lyophilized cMSC conditioned-medium were compared with conditioned-medium from non-MSC cells (corneal epithelial cells) using scratch assay. To evaluate the anti-inflammatory effects of fresh and lyophilized cMSC conditioned-media, macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the conditioned-media and measuring the expression of inflammatory genes. In vivo wound healing effects of fresh and lyophilized cMSC conditioned-media were assessed in a murine model of cornea epithelial injury. RESULTS: Both fresh and lyophilized cMSCs-derived conditioned-medium induced significantly faster closure of in vitro epithelial wounds compared to conditioned-medium from non-MSC cells (P

Purpose: The objective of this study was to describe the short-term results of allogenic transplantation of limbal stem cells expanded on amniotic membrane for the ocular surface reconstruction. Methods: Prospective nonrandomized, nonmasked study in a single ophthalmological center. Ten patients with bilateral total limbal stem cell deficiency (LSCD) were included. Expression and presence of ABCB5 and Δp63α in amniotic membrane-cultured limbal epithelial stem cells were analyzed, in relationship with clinical changes after allogenic transplantation. An objective evaluation was performed to determine corneal transparency and superficial vascularization. Results: In a median follow-up time of 11.6 months, 7 patients (70%) were considered as failure compared with the preoperative status. ABCB5 and Δp63α are expressed in similar amount in the limbal epithelial cells expanded in vitro and transplanted in patients with bilateral LSCD. Conclusions: Transplantation of allogenic epithelial limbal cells expanded in amniotic membrane could be considered in patients with LSCD due to burns or congenital etiologies such as aniridia, but its benefit is limited for patients with immunologic diseases.

Purpose To study the efficacy of interferon alfa-2b (IFN-a2b) on pigmented ocular surface squamous neoplasia (p-OSSN) and assess the resolution of the pigment to the treatment. Methods A retrospective case series of 8 tumors in 7 patients. Results The mean age at diagnosis of p-OSSN was 65 years (median, 61 years; range, 51-84 years), and all patients were men. The mean duration of symptoms was 2 months (median, 1 month; range, 1-4 months). One patient had 2 distinct lesions in the same eye. Tumor epicenter was located at the limbus (n = 5) or bulbar conjunctiva (n = 2). Complexion-associated melanosis was noted in all eyes. The mean basal dimension of the tumor was 8 mm (median, 7 mm; range, 5-12 mm). The mean % of tumor pigmentation was 47% (median, 30%; range, 10%-100%). The treatment details included topical IFN-a2b (n = 1) or a combination of topical and subconjunctival injection of IFN-a2b (n = 7). All patients with p-OSSN showed excellent response to IFN-a2b with complete tumor regression and resolution of tumor-associated pigment with a mean number of 2 subconjunctival IFN-a2b injections (median, 2; range, 0-3) and topical IFN-a2b for an average of 2 months (median, 2 months; range, 1-3 months). There was no change in the complexion-associated melanosis with IFN-a2b. Conclusions IFN-a2b is very effective in the management of p-OSSN. There is a complete resolution of the pigment along with the tumor.