Vismodegib as an adjuvant treatment for periorbital basal cell carcinoma: a case report and review of literature.

Background: Basal cell carcinoma (BCC) is the most common cancer type worldwide. Although there are several treatment options for the treatment of BCC, selecting the best treatment option for periorbital BCC is challenging and it varies case by case. More than half of periocular BCC cases initially occur on the inner angle and lower lid. The treatment options for BCC include radical surgical excision using Mohs micrographic technique, radiotherapy, neoadjuvant vismodegib, imiquimod, and combination therapy followed by reconstruction for functionality and aesthetic outcome. Selection of each treatment varies based on the severity and extension of BCC. Case Description: We report a case of periorbital BCC invading the left lower eyelid in a 50-year-old Caucasian male which was initially excised a few years ago, and, following recurrence, the patient underwent Mohs micrographic surgery. Due to a recurrence after Mohs micrographic surgery, treatment with oral vismodegib was started, which led to near-total tumor shrinkage. To determine the outcome of periorbital BCC treated with vismodegib, we reviewed the literature on the periorbital BCC treated with vismodegib, their follow-up period, outcome, and whether they were metastatic or had recurrence. Conclusions: Neoadjuvant vismodegib, followed by surgery excision, such as Mohs micrographic surgery, has shown a promising clinical and aesthetic outcome in the treatment of periorbital BCC.

Posterior Segment Manifestations of Syphilis and Correlation With Serologic Markers of Infection.

BACKGROUND AND OBJECTIVE: Retrospective analysis correlating serologic titers of ocular syphilis with posterior segment manifestations. PATIENTS AND METHODS: This study consisted of 40 patients (80 eyes imaged, 68 affected) with positive rapid plasma reagin (RPR) and Treponema Pallidum immunoglobulin G. We collected demographic and presentation data including HIV status, absolute CD4 count, RPR, cerebrospinal fluid-venereal disease research laboratory (CSF-VDRL) test, and retinal zone. We categorized imaging into syphilitic outer retinopathy (SOR), acute syphilitic posterior placoid chorioretinopathy, retinitis/chorioretinitis (RC), and papillitis. Multivariate analysis correlated HIV status, RPR, and VDRL titers with posterior segment findings and zone. RESULTS: Mean age of 42.8 ± 10.7 years, with 70% male patients. Presenting visual acuity (logMAR) 0.66 ± 0.74 did not correlate with RPR, nor was it associated with papillitis, RC, or acute syphilitic posterior placoid chorioretinopathy. Higher RPR (≥ 1:128) positively associated with SOR (P = 0.031) and zone 1 (odds ratio [OR], 1.62; P = 0.02), but negatively associated with zone 2 (OR 0.35; P = 0.005). HIV positivity increased RC odds (OR, 4.45; P = 0.047). CONCLUSION: Higher RPR correlated with SOR and zone 1, whereas HIV positivity correlated with RC. [Ophthalmic Surg Lasers Imaging Retina 2024;55:511-516.].

Composition of the gut microbiome, role of diet, lifestyle, and antioxidant therapies in diabetes mellitus and diabetic retinopathy.

The gut microbiome is a complex ecosystem in the gastrointestinal tract composed of trillions of bacteria, viruses, fungi, and protozoa. Disruption of this delicate ecosystem, formally called "dysbiosis", has been linked to a variety of metabolic and inflammatory pathologies. Several studies have focused on abnormal microbiome composition and correlated these findings with the development of type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR). However, given the complexity of this ecosystem, the current studies are narrow in design and present variable findings. Composition of the gut microbiome in patients with DR significantly differs from patients with diabetes without retinopathy as well as from healthy controls. Additionally, the gut microbiome has been shown to modify effects of medication, diet, exercise, and antioxidant use on the development and progression of DR. In this paper, we present a comprehensive review of literature on the effect of oxidative stress, antioxidant therapies, and dysbiosis on DR.

Sealed Unilateral Full-Thickness Macular Hole with Amniotic Membrane Graft in a Patient with Alport Syndrome: A Case Report.

We present a case of unilateral full-thickness macular hole (MH) successfully repaired with an amniotic membrane (AM) graft in a patient with Alport syndrome. A 58-year-old Asian female with past medical history of Alport syndrome diagnosed at early stage, presented with a 5-week history of vision loss in her right eye. Examination of her eyes showed normal retinal vessels and an MH measuring 1,300 µm in basal diameter, 806 µm in minimum linear diameter, and 490 µm in height in the right eye and macular thinning with laser scars inferiorly in the left eye. The patient underwent 23-g pars plana vitrectomy with intraocular lens explantation. After multiple unsuccessful attempts in inducing a posterior vitreous detachment around the optic nerve and in the posterior pole, a 1 mm AM graft placed on the MH and the edges tucked under the edges of the hole using a bimanual technique. Five months after surgery, the MH remained sealed with improved final vision. MHs are rare manifestations of Alport syndrome, and surgical treatment of Alport syndrome-associated MHs is challenging. However, further studies to explore new techniques using AM are needed.

Retinal Detachment Associated with Retinal Dialysis: Clinical Features and Outcomes of Surgery in a 10-Year Study.

PURPOSE: To report the surgical approaches and outcomes in patients undergoing surgery for retinal detachment associated with retinal dialysis. DESIGN: Retrospective, consecutive case series. SUBJECTS: All patients who underwent surgery for retinal detachment secondary to retinal dialysis between January 1, 2012, and January 1, 2022. METHODS: Retrospective consecutive case series. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), single-operation success rate. RESULTS: The study cohort included 60 eyes of 58 patients with a mean age of 26.4 (standard deviation, 13.0) years. Males comprised 49 (84.5%) patients. Known trauma occurred in 35 (61.4%) cases. Initial surgical management included scleral buckling (SB) in 49 (81.7%) eyes and combined SB and pars plana vitrectomy (PPV) in 11 (18.3%) eyes. Preoperative BCVA correlated with BCVA at last follow-up visit (r = 0.66; P < 0.001). At last visit, the SB group had a mean logarithm of the minimum angle of resolution BCVA of 0.36 (20/46) and a single-operation success rate of 76.9% at 6 months, whereas the SB/PPV group had a mean logarithm of the minimum angle of resolution BCVA of 1.08 (20/238) and single-operation success rate of 77.8% (P = 0.04 and P = 0.96, respectively). Six eyes in the SB/PPV group received silicone oil tamponade. In eyes with at least 1 year of follow-up, 4 (14.8%) in the SB group and 6 (100%) in the SB/PPV group developed a visually significant cataract requiring cataract surgery (P < 0.001). CONCLUSIONS: Retinal detachment associated with retinal dialysis is typically associated with trauma and more often occurs in young male patients. The current study confirms that SB without PPV is an effective initial treatment strategy for most patients with retinal dialysis and has a low rate of cataract formation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Artificial intelligence in retinal image analysis: Development, advances, and challenges.

Modern advances in diagnostic technologies offer the potential for unprecedented insight into ophthalmic conditions relating to the retina. We discuss the current landscape of artificial intelligence in retina with respect to screening, diagnosis, and monitoring of retinal pathologies such as diabetic retinopathy, diabetic macular edema, central serous chorioretinopathy, and age-related macular degeneration. We review the methods used in these models and evaluate their performance in both research and clinical contexts and discuss potential future directions for investigation, use of multiple imaging modalities in artificial intelligence algorithms, and challenges in the application of artificial intelligence in retinal pathologies.

Pars Plana Vitrectomy for Retained Lens Fragments After Cataract Surgery: Outcomes Based on Timing of Surgery.

Purpose: To evaluate the outcomes and complications in patients with retained lens fragments (RLF) after cataract surgery, comparing those who received pars plana vitrectomy (PPV) on the same day, within 1 week, or later than 1 week after cataract surgery. Patients and Methods: Retrospective case series of all patients who underwent PPV for RLF at Bascom Palmer Eye Institute between January 1, 2012 and September 30, 2020. Individuals with less than 3 months of follow-up, chronic uveitis, congenital cataract, previtrectomy retinal detachment (RD), and severe trauma were excluded. All analyses for categorical and binary variables used chi-squared tests. Analyses for continuous variables were performed using multivariate analyses of covariance, adjusting for differences in baseline visual acuity before cataract surgery. Results: The study included 246 eyes of 246 patients. The timing distribution included the following: 140 (57%) eyes underwent same-day PPV, 33 (13%) eyes underwent same-week PPV, and 73 (30%) eyes underwent PPV after 1 week (up to 90 days). When all eyes were included in analysis, there were no statistically significant differences in mean best-corrected visual acuity (BCVA) between groups at last follow-up examination (P = 0.07). When only eyes without known pre-existing ocular disease (N = 157) were included in analysis, there were no differences in mean BCVA between groups at all postoperative timepoints (P > 0.05). The rate of RD did not differ between groups when eyes with and without pre-existing ocular disease were analyzed (P > 0.05). Conclusion: In the current study, there were no statistically significant differences in postoperative BCVA or rates of RD at last follow-up examination in eyes undergoing PPV for RLF on the same day, within 1 week, or later than 1 week after cataract surgery.

Visual outcomes and postoperative complications of eyes with dropped lens fragments during cataract surgery: multicenter database study.

PURPOSE: To analyze the visual outcomes and postoperative complications of phacoemulsification cataract surgery in eyes with posterior capsule rupture (PCR) and dropped lens fragments (DLFs) in comparison with a reference group with uneventful surgery. SETTING: 8 UK National Health Service departments. DESIGN: Retrospective comparative nonrandomized study. METHODS: Demographic, medical history, and ocular examination data were automatically extracted from the electronic records. The main outcome variables were postoperative visual acuity (VA), and the development of postoperative cystoid macular edema (CME) as well as rhegmatogenous retinal detachment (RRD) and epiretinal membrane (ERM) requiring surgery. RESULTS: The analysis included 175 589 eyes in the reference group, 2751 eyes in the PCR group, and 519 eyes in the DLF group. During all postoperative intervals, the mean VA in the DLF and PCR groups was significantly worse than the reference group ( P < .001). On multivariate analysis, the odds of having a VA ≤0.3 logMAR at 4 to 12 weeks postoperatively among eyes with DLF and PCR were 88% and 73% lower than the reference group ( P < .001). More eyes developed CME in the DLF and PCR groups ( P < .001). The odds of requiring RRD and ERM surgery were 3.6 and 2.1 times higher in the DLF group, and 1.8 and 1.3 times higher in the PCR group, respectively, as compared with the reference group. CONCLUSIONS: Eyes undergoing phacoemulsification complicated by PCR, and more so with DLF, have worse visual outcomes and higher chances of CME, ERM, and RRD when compared with uneventful surgery.

Gut microbiome and diabetic retinopathy.

During the last decades, the incidence of diabetes and a variety of complications such as diabetic retinopathy (DR) and cardiovascular diseases have been increased exponentially. Gut bacterial composition -microbiota - has been associated with the pathobiology of many inflammatory and metabolic disorders such as diabetes. Gut microbiota plays a crucial role in preserving the metabolic and immune homeostasis, protecting against pathogens and regulating host immunity; however, gut microbiome ecosystem can be altered by lifestyle, cigarette smoking, dietary patterns, and oxidative stress.Herein, we present a hypothesis on the potential complex association between gut microbiota and DR as one of the microvascular complications of diabetes.

Intraoperative complications and visual outcomes of cataract surgery in patients with retinal vein occlusion: multicenter database study.

PURPOSE: To compare the visual outcomes and the rate of intraoperative complications in eyes with and without retinal vein occlusion (RVO) after phacoemulsification over a period of 15 years in a real-world clinical setting. SETTING: 8 independent U.K. National Health Service ophthalmology departments. DESIGN: Retrospective, multicenter cohort study. METHODS: Eyes were classified based on the presence or absence of RVO. For analyzing visual acuity (VA) and the incidence of postoperative cystoid macular edema, eyes with any copathology, combined ocular surgical procedures, and intraoperative complications, or of diabetic patients were excluded. RESULTS: Of 178 856 eyes, 1796 eyes with RVO preoperatively and 177 060 eyes without RVO were allocated to the RVO group and the reference group, respectively. Cataract surgery in eyes with RVO was associated with an improvement in the mean VA of 0.35 logMAR (3 to 4 Snellen lines), and a substantial gain (≥0.30 logMAR units [3 Snellen lines]) was achieved in 55.10% of eyes at 4 to 12 weeks postoperatively. The mean postoperative VA was worse in eyes with RVO compared with that in eyes without RVO at 4 to 12 weeks (logMAR 0.40 vs 0.12 [20/50 vs 20/25]; P < .0001). The proportion of eyes achieving a visual gain of ≥ 0.3 logMAR (3 Snellen lines) was also lower in eyes with RVO (55.10% vs 64.55%; P = .0076). There was no statistically significant difference in posterior capsule rupture rates between the 2 groups (1.73% vs 1.72%; P = .9741). CONCLUSIONS: Although postoperative vision improved significantly in eyes with RVO after cataract surgery, this improvement was worse than that achieved by eyes without RVO.

DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION AFTER TREATMENT WITH PHOTODYNAMIC THERAPY IN A 5-YEAR-OLD FEMALE WITH CHOROIDAL OSTEOMA.

PURPOSE: To describe a patient with a choroidal osteoma treated with photodynamic therapy to prevent tumor growth in whom choroidal neovascularization (CNV) developed after being treated with photodynamic therapy. METHODS: Case report. RESULTS: A 5-year-old Hispanic woman presented with an asymptomatic choroidal osteoma, temporal to the macula of her right eye. According to the patient's mother, her medical, surgical, and family history was unremarkable. At examination, best-corrected visual acuity was 20/30 in both eyes. After 11 months of follow-up, signs of tumor growth toward the fovea without any signs of CNV was noted. Photodynamic therapy was performed to prevent invasion of the foveola. Two months thereafter, the patient developed CNV in the macula region in the right eye, decreasing visual acuity to 20/200. The patient was treated with four total intravitreal injections of 1.25 mg of bevacizumab over 24 weeks, which resulted in inactivation of the CNV and improved visual acuity to 20/20. Choroidal neovascularization had been never reported in her past history and her follow-up visits over 7 years. In addition, no evidence of recurrent neovascular activity or tumor growth was reported. CONCLUSION: Choroidal osteoma is a benign tumor that can result in vision-threatening complications, caused by tumor growth and tumor decalcification. Photodynamic therapy is an effective modality in inducing choroidal osteoma decalcification and stabilization; however, CNV due to reperfusion following photodynamic therapy can be seen in the retina.

Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair.

Purpose: Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow-derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits. Methods: Human bone marrow-derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes. Results: The viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1% ± 2.1% and 94.9% ± 1.3%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5% ± 12.1% in epithelial cells co-cultured with MSCs compared with 40.8% ± 23.1% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100% corneal wound closure compared with 79.9% ± 5.5% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection. Conclusions: Subconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models. Translational Relevance: These results provide preclinical data to support a phase I clinical study.

Dose-dependent therapeutic effects of topical 1,25 OH-vitamin D3 on corneal wound healing.

Conflicting results have been reported regarding the effects of 1,25 OH-vitamin D3 on corneal wound healing. Therefore, we undertook this study to determine whether the observed differences are dose related. The dose-dependent effects of 1,25 OH-vitamin D3 on corneal wound healing were evaluated using scratch assays on human corneal limbal-epithelial cells (HCLEs) and in vivo mouse corneal epithelial debridement. To evaluate the anti-inflammatory effects of 1,25 OH-vitamin D3, macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the 10-6 M, 10-7 M and 10-8 M 1,25 OH-vitamin D3. 10-7 M 1,25 OH-vitamin D3 induced faster scratch wound closure compared with the other concentrations of 1,25 OH-vitamin D3 tested (10-6 M and 10-8 M), and 0.02% ethanol as a control (85.8 ± 2.6%, 33.9 ± 6.74%, 32.6 ± 3.35%, and 31.6 ± 3.99%, respectively, P < 0.0001). Single-time treatment with 10-7 M 1,25 OH-vitamin D3 also significantly improved the healing of mouse corneal epithelial wound compared to multiple treatments and control (74.1 ± 17.3% vs. 52.4 ± 11.6% and 45.8 ± 13.4%, respectively). Polyinosinic: polycytidylic acid (poly [I:C])-stimulated macrophage cells and 10-7 M 1,25 OH-vitamin D3 significantly decreased gene expression of ICAM1, TLR3, IL6, IL8, and TNFα (P < 0.0001). Our results suggest the dose-dependent therapeutic effect of 1,25 OH-vitamin D3 in corneal wound healing which can be potentially used as a non-invasive option in the treatment of corneal wounds.

Regression of corneal neovascularization: Adiponectin versus bevacizumab eye drops.

PURPOSE: Comparing the effect of adiponectin versus bevacizumab in decreasing corneal neovascularization. METHODS: This study was conducted on 30 eyes of 30 New Zealand Albino male rabbits. Corneal neovascularization was induced by a single 7-0 silk suture 2 mm long and 1 mm in front of the limbus for 2 weeks. Rabbits were randomly divided into three groups of adiponectin (20 µg/mL), bevacizumab (5 mg/mL) and artificial tears. The treatments continued up to 14 days. RESULTS: At the end of 14 days, the average length of vessels in rabbits treated with adiponectin, bevacizumab and control groups decreased from 2.12 ± 0.32 mm to 0.89 ± 0.46 mm (57.68% ± 19.98%) (P < 0.001), 2.30 ± 0.41 mm to 1.30 ± 0.58 mm (42.49% ± 27.17%) (P = 0.048) and from 2.12 ± 0.44 mm to 1.81 ± 0.42 mm (14.81% ± 5.64%) (P = 0.112), respectively. The length of vessels decreased 57.68% ± 19.98% and 42.49% ± 27.17% in adiponectin versus bevacizumab groups, respectively (P = 0.527). The average surface area of vessels in rabbits treated with adiponectin, bevacizumab and control groups reduced from 5.02 ± 1.50 mm2 to 1.40 ± 0.75 mm2 (70.64% ± 17.76%) (P < 0.001) 0.34 ± 1.1 mm2 to 2.80 ± 1.04 mm2 (48.24% ± 19.23%) (P = 0.039) and 5.12 ± 2.92 mm2 to 4.4 ± 2.55 mm2 (14.68% ± 4.19%) (P = 0.117). Mean surface area of vascularization decreased 70.64% ± 17.76% and 48.24% ± 19.23% in adiponectin versus bevacizumab, respectively (P = 0.013). CONCLUSIONS: The results of this study suggest that topical adiponectin can decrease recent corneal neovascularization.

Effect of dietary modification and antioxidant supplementation on intraocular pressure and open-angle glaucoma.

Primary open-angle glaucoma (POAG) is an age-dependent, intraocular pressure (IOP)-related degeneration of the retinal ganglion cells (RGC). At present, IOP is the only modifiable factor that has been identified to prevent glaucomatous vision loss. Though the pathogenesis of glaucomatous optic neuropathy is still not well understood, increasing evidence suggests oxidative stress may contribute to the induction and progression of glaucoma. Furthermore, antioxidant use may be protective against glaucoma through various mechanisms, including reducing IOP, preserving vascular health, and preventing ganglion cell loss. This article provides a comprehensive review of the effect of oxidative stress, diet, and antioxidant therapy on IOP and open-angle glaucoma.

Update on the pathogenesis and management of ocular rosacea: an interdisciplinary review.

PURPOSE: Rosacea is one of the most common conditions affecting the ocular surface. The purpose of this review is to provide an update on the pathogenesis and treatment of rosacea based on the dermatology and ophthalmology literatures. METHODS: Literature searches were conducted for rosacea and ocular rosacea. Preference was given to systematic reviews, meta-analysis, case-controlled studies, and documented case reports while excluding poorly documented case studies and commentaries. The data were examined and independently analyzed by more than two of the authors. RESULTS: Rosacea is a complex inflammatory condition involving the pilosebaceous unit. Its underlying mechanism involves an interplay of the microbiome, innate immunity, adaptive immunity, environmental triggers, and neurovascular sensitivity. The latest classification of rosacea includes three dermatologic subgroups and a fourth subgroup, ocular rosacea. Ocular rosacea clinically displays many features that are analogous to the cutaneous disease, such as lid margin telangiectasia and phlyctenulosis. The role of environmental triggers in the exacerbation of ocular rosacea appears to be understudied. While lid hygiene and systemic treatment with tetracycline drugs remain the mainstay of treatment for ocular rosacea, newer dermatologic targets and therapies may have potential application for the eye disease. CONCLUSIONS: Ocular rosacea appears to embody many of the manifestation of the dermatologic disease. Hence, the basic pathophysiologic mechanisms of the ocular and cutaneous disease are likely to be shared. Better understanding of the ocular surface microbiome and the immunologic mechanisms, may lead to novel approaches in the management of ocular rosacea.

The Effect of Mesenchymal Stem Cell Secretome on Corneal Endothelial Cell Preservation in an Oxidative Injury Model.

PURPOSE: To describe a reproducible oxidative injury model in ex vivo porcine corneas and to investigate the effects of corneal mesenchymal stem cell (Co-MSC) secretome and specific factors on the preservation of corneal endothelium after oxidative injury. METHODS: Porcine corneas underwent vital staining with trypan blue and alizarin red with different concentration and time points. Ex vivo porcine corneas were exposed (endothelial side) to varied concentrations of hydrogen peroxide. After injury, 3 groups of 5 corneas underwent treatment with secretome from either a wild-type (WT) murine Co-MSC, a pigment epithelium derived factor (PEDF) knock out (K/O) murine Co-MSC, or basal media for 4 hours at 37°C. The viability of the endothelium was evaluated using the optimized vital staining protocol. RESULTS: The optimal vital staining was achieved with 0.4% trypan blue for 60 seconds and 0.5% alizarin red for 90 seconds. The optimal oxidative injury (for consistency and level of damage) was obtained with 1% hydrogen peroxide for 15 seconds. Treatment with both WT Co-MSC and PEDF K/O Co-MSC secretome significantly reduced the endothelial damage compared with control (17.2% ± 10.0%, 33.5% ± 11.6%, and 68% ± 17%, respectively, P < 0.01). The WT Co-MSC secretome was significantly more effective compared with PEDF K/O Co-MSC secretome (P < 0.05). CONCLUSIONS: A reproducible model of vital staining and oxidative injury is described for studying porcine corneal endothelial survival. Our results demonstrate a beneficial role of a corneal MSC secretome in reducing oxidative damage to the corneal endothelium. In addition, it suggests a potential role for PEDF in this process.

Reproducible Derivation and Expansion of Corneal Mesenchymal Stromal Cells for Therapeutic Applications.

Purpose: A reproducible protocol for the production of corneal mesenchymal stem/stromal cells (cMSCs) is necessary for potential clinical applications. We aimed to describe successful generation and expansion of cMSCs using an explant method. Methods: Corneoscleral rims of human cadaveric eyes were divided into four pieces and used as explants to allow outgrowth of cMSCs (passage 0, or P0). The cells were subcultured at a 1:10 ratio until passage 5 (P5). The characteristics as well as therapeutic effects of expanded cMSCs were evaluated both in vitro, using a scratch assay, and in vivo using epithelial debridement and chemical injury mouse models. Results: All explants demonstrated outgrowth of cells by 7 days. Although the initial outgrowth included mixed mesenchymal and epithelial cells, by P1 only cMSCs remained. By subculturing each flask at a ratio of 1:10, the potential yield from each cornea was approximately 12 to 16 × 1010 P5 cells. P5 cMSCs demonstrated the cell surface markers of MSCs. The secretome of P5 cMSCs induced faster closure of wounds in an in vitro scratch assay. Subconjunctival injection of P5 cMSCs in mouse models of mechanical corneal epithelial debridement or ethanol injury led to significantly faster wound healing and decreased inflammation, relative to control. Conclusions: cMSCs can be reproducibly derived from human cadaveric corneas using an explant method and expanded with preservation of characteristics and corneal wound healing effects. Translational Relevance: The results of our study showed that cMSCs produced using this scheme can be potentially used for clinical applications.

Therapeutic Effects of Lyophilized Conditioned-Medium Derived from Corneal Mesenchymal Stromal Cells on Corneal Epithelial Wound Healing.

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 < .0001). Treating stimulated macrophages with fresh or lyophilized cMSCs-derived conditioned-media significantly decreased the expression of inflammatory genes compared to control (P < .0001). Murine corneal epithelial wounds were healed by 87.6 ± 2.7% and 86.2 ± 4.6% following treatment with fresh and lyophilized cMSC conditioned-media, respectively, while the control was healed by 64.7 ± 16.8% (P < .05). Conclusion: Lyophilized cMSC-derived conditioned-medium is as effective as fresh conditioned-medium in promoting wound healing and modulating inflammation. The results of this study support the application of lyophilized cMSCs-derived conditioned-medium, which allows for more extended storage, as a promising non-invasive option in the treatment of corneal wounds.

Oculocerebrorenal syndrome of Lowe: Survey of ophthalmic presentations and management.

BACKGROUND: Lowe syndrome is a rare X-linked disease that is characterized by renal dysfunction, developmental delays, congenital cataracts and glaucoma. Mutations in the oculocerebral renal syndrome of Lowe (OCRL) gene are found in Lowe syndrome patients. Although loss of vision is a major concern for families and physicians who take care of Lowe syndrome children, definitive cause of visual loss is still unclear. Children usually present with bilateral dense cataracts at birth and glaucoma, which occurs in more than half of cases, either concurrently or following cataract surgery. MATERIALS AND METHODS: A retrospective review was conducted on the prevalence and characteristics of ocular findings among families of patients with Lowe syndrome with 137 uniquely affected individuals. RESULTS: Of 137 patients, all had bilateral congenital cataracts. Nystagmus was reported in 69.3% of cases, glaucoma in 54.7%, strabismus in 35.0%, and corneal scar in 18.2% of patients. Glaucoma was reported as the most common cause of blindness (46%) followed by corneal scars (41%). Glaucoma occurred in 54.7% of patients and affected both eyes in the majority of cases. Of these patients, 55% underwent surgery for glaucoma, while the remaining patients used medications to control their eye pressure. Timolol and latanoprost were the most commonly used medications. Although trabeculectomy and goniotomy are commonly used for pressure management, aqueous tube shunts had the best outcomes. CONCLUSION: Ocular manifestations in individuals with Lowe syndrome and carriers with OCRL mutation are reported which may help familiarize clinicians with the ocular manifestations and management of a rare and complex syndrome.