In vivo study to assess dosage of allogeneic pig retinal progenitor cells: Long-term survival, engraftment, differentiation and safety.

Despite notable efforts and significant therapeutical advances, age-related macular degeneration remains the single most common reason for vision loss. Retinal progenitor cells (RPCs) are considered promising candidates for cellular treatments that repair and restore vision. In this allogenic study, the phenotypic profile of pig and human RPCs derived using similar manufacturing processes is compared. The long-term (12-week) survival of green fluorescent protein-pig retinal progenitor cells GFP-pRPC after subretinal transplantation into normal miniature pig (mini-pig) retina is investigated. Human eyes are both anatomically and physiologically mimicked by pig eyes, so the pig is an ideal model to show an equivalent way of delivering cells, immunological response and dosage. The phenotypic equivalency of porcine and clinically intended human RPCs was established. Thirty-nine mini-pigs are used in this study, and vehicle-injected eyes and non-injected eyes serve as controls. Six groups are given different dosages of pRPCs, and the cells are found to survive well in all groups. At 12 weeks, strong evidence of integration is indicated by the location of the grafted cells within the neuro-retina, extension of processes to the plexiform layers and expression of key retinal markers such as recoverin, rhodopsin and synaptophysin. No immunosuppression is used, and no immune response is found in any of the groups. No pRPC-related histopathology findings are reported in the major organs investigated. An initial dose of 250 k cells in 100 µl of buffer is established as an appropriate initial dose for future human clinical trials.

FULL-THICKNESS MACULAR HOLE SIZE BY HYPERTRANSMISSION SIGNAL ON SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To assess the full-thickness macular hole (FTMH) size using the choroidal hypertransmission signal on spectral-domain optical coherence tomography and to compare this method to the standard aperture measurement of the minimum aperture size at the level of the neurosensory retina. DESIGN: Cross-sectional study of retrospective data. METHODS: Eyes with FTMH imaged on spectral-domain optical coherence tomography were included. Two independent masked graders used the device's built-in caliper tool to measure the FTMH minimum aperture size at the level of the neurosensory retina and the size of the corresponding hypertransmission signal below the level of the retinal pigment epithelium/Bruch membrane complex. To assess the reproducibility of the hypertransmission measurement in tilted scans, two measurements were obtained and compared; the first was traced parallel to the retinal pigment epithelium (parallel hypertransmission), and the second was horizontal to the image frame (horizontal hypertransmission), both using Image J software. RESULTS: A total of 31 eyes were enrolled. The mean FTMH minimum aperture size was smaller compared with both the choroidal parallel hypertransmission and horizontal hypertransmission measurements (mean ± SD: 335.7 ± 139.5 µm, 376.7 ± 150.6 µm, 375.1 ± 150.0 µm, respectively. P < 0.001 for both comparisons). CONCLUSION: The proposed hypertransmission measurement is a feasible and reproducible alternative to assess FTMH size and could provide the basis for an automated FTMH measurement on cross-sectional spectral-domain optical coherence tomography scans, as presented in this study, or on the spectral-domain optical coherence tomography volumetric data set by using an en face projection.

VISUALIZATION OF CHOROIDAL NEOVASCULARIZATION USING TWO COMMERCIALLY AVAILABLE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DEVICES.

PURPOSE: To compare the sensitivity of detection and the measured size of choroidal neovascularization (CNV) on two commercially available spectral domain optical coherence tomography angiography (OCTA) devices, the Optovue RTVue XR Avanti with AngioVue and the Zeiss Cirrus HD-OCT with AngioPlex. METHODS: Patients with CNV lesions were imaged consecutively on both OCTA devices on the same day of their visit. 3 × 3 mm and 6 × 6 mm scans centered at the fovea were obtained. Two independent masked readers evaluated the OCTA images for CNV identification and its area measurements. RESULTS: No significant differences were observed between the 2 OCTA devices in CNV area measurements on their 3 × 3 mm and 6 × 6 mm scans. However, there was suboptimal performance of their automated segmentation algorithms as compared to manually adjusted segmentation for visualizing CNV lesions. CONCLUSION: There was no significant difference in the size of the CNV lesion as measured on either commercially available spectral domain OCTA device. Both devices were comparable in their detection of CNV lesions on manual adjustment of segmentation lines. However, their automated segmentation algorithms need improvement to allow for accurate measurement of CNV lesions for routine clinical application.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY TO DETECT MACULAR CAPILLARY ISCHEMIA IN PATIENTS WITH INNER RETINAL CHANGES AFTER RESOLVED DIABETIC MACULAR EDEMA.

PURPOSE: To compare foveal vascular anatomy between patients with and without disorganization of retinal inner layers (DRILs) after resolved diabetic macular edema using optical coherence tomography angiography (OCTA). METHODS: Twenty-four eyes of 21 age- and sex-matched patients with resolved diabetic macular edema were included in this retrospective, cross-sectional study. All eyes were imaged with enhanced high-definition line or cross-line structural B scans and 3 × 3-mm OCTA scans. Optical coherence tomography B scans were analyzed for the presence of DRIL, and based on this, eyes were classified as either DRIL present or DRIL absent. The foveal avascular zone area on OCTA was compared between patients with and without DRIL. The foveal avascular zone area was correlated with visual acuity. RESULTS: Nine eyes with DRIL and resolved diabetic macular edema were compared with 15 control eyes without DRIL and resolved diabetic macular edema. Area of ischemia on OCTA scans corresponded to the area of DRIL as determined on OCT B scans. The foveal avascular zone area in full retina as well as superficial and deep retinal plexuses OCTA slabs were significantly larger in patients with DRIL as compared to those without DRIL (P = 0.005, P < 0.001, and P = 0.004, respectively). The larger foveal avascular zone in full retinal segmentation (r = 0.72, P = 0.03) and superficial plexus (r = 0.74, P = 0.02) were positively correlated with lower visual acuity. CONCLUSION: Optical coherence tomography angiography can visualize retinal ischemia in patients with and without DRIL. Correspondence of impaired blood flow with DRIL suggests that retinal ischemia and loss of normal vasculature contributes to DRIL.

CLINICAL TRIAL ENDPOINTS FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To describe qualitative and quantitative optical coherence tomography (OCT) angiography (OCTA) parameters for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and their applicability as potential clinical trial endpoints. METHODS: A review of current literature related to the topic of OCTA and AMD. RESULTS: There are a number of promising OCTA parameters that can be used to diagnose the presence of CNV and to monitor the activity and progression of the lesion, pre- and post-treatment morphological characteristics, CNV dimensions, and automated quantitative parameters such as vessel density. CONCLUSION: The OCTA parameters described in this review have promise for the future development of clinical trial endpoints, but require further validation before they can be widely used.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS CHORIOCAPILLARIS ALTERATIONS IN EYES WITH NASCENT GEOGRAPHIC ATROPHY AND DRUSEN-ASSOCIATED GEOGRAPHIC ATROPHY.

PURPOSE: To investigate choriocapillaris (CC) alteration in patients with nascent geographic atrophy (nGA) and/or drusen-associated geographic atrophy (DAGA) using swept-source optical coherence tomography angiography (OCTA). METHODS: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric swept-source optical coherence tomography angiography over 6 mm × 6 mm fields of view in patients with nGA and/or DAGA. The resulting optical coherence tomography (OCT) and OCTA data were analyzed using a combination of en face and cross-sectional techniques. Variable interscan time analysis (VISTA) was used to differentiate CC flow impairment from complete CC atrophy. RESULTS: A total of 7 eyes from 6 patients (mean age: 73.8 ± 5.7 years) were scanned. Seven areas of nGA and three areas of DAGA were identified. Analysis of cross-sectional OCT and OCTA images identified focal alterations of the CC underlying all seven areas of nGA and all three areas of DAGA. En face OCTA analysis of the CC revealed diffuse CC alterations in all eyes. Variable interscan time analysis processing suggested that the observed CC flow alterations predominantly corresponded to flow impairment rather than complete CC atrophy. CONCLUSION: The OCTA imaging of the CC revealed focal CC flow impairment associated with areas of nGA and DAGA, as well as diffuse CC flow impairment throughout the imaged field. En face OCT analysis should prove useful for understanding the pathogenesis of nGA and DAGA and for identifying the formation of nGA and DAGA as endpoints in therapeutic trials.

Contemporary retinal imaging techniques in diabetic retinopathy: a review.

Over the last decade, there has been an expansion of imaging modalities available to clinicians to diagnose and monitor the treatment and progression of diabetic retinopathy. Recently, advances in image technologies related to OCT and OCT angiography have enabled improved visualization and understanding of this disease. In this review, we will describe the use of imaging techniques such as colour fundus photography, fundus autofluorescence, fluorescein angiography, infrared reflectance imaging, OCT, OCT-Angiography and techniques in adaptive optics and hyperspectral imaging in the diagnosis and management of diabetic retinopathy.

Evaluation of Refraction Outcomes From the QuickSee Wavefront Autorefractor Versus Subjective Clinical Refractometry in Children With Restricted Access to Eye Care in Amazonas, Brazil.

Background This study compared the refraction measurements of the QuickSee wavefront autorefractor with those from clinical refraction measurements in preschool and elementary school children from public schools in Amazonas, Brazil. Methodology Refractometry was performed on 368 eyes from 368 healthy Brazilian public school students aged 4 to 7 years using both the QuickSee and subjective clinical methods under cycloplegia. Only right-eye data were analyzed. The results were converted into spherical equivalents and vector magnitudes for comparison. Results The difference in spherical equivalents between QuickSee and subjective clinical refractometry under cycloplegia was +0.38 ± 0.60 Diopters (D) (p < 0.0001). Along the 90° axis, the vector difference was +0.20 ± 0.33 D (p < 0.0001), and the oblique vector difference was +0.03 ± 0.22 D (p = 0.0395). Conclusions While a statistically significant difference was found between the QuickSee and subjective clinical refractometry results, the difference was not clinically meaningful. The strong agreement between these methods supports the utility of QuickSee as an effective tool for refractive assessment in children with limited access to eye care. These findings provide confidence in using QuickSee in public school settings as a reliable alternative for vision screening.

Autologous Serum for the Treatment of Macular Holes: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy and safety of autologous human serum as an adjuvant agent in pars plana vitrectomy (PPV) for macular holes (MH). Thus, a comprehensive search was conducted across PubMed, Web of Science, Embase, and the Cochrane Library databases up to August 20th, 2023. The inclusion criteria targeted randomized clinical trials (RCTs) or non-RCTs that compared the use of autologous serum in vitrectomy for MH with the same procedure without the serum. The outcomes were MH closure rates and postoperative complications such as retinal detachment and cataracts. Odds ratios (OR) and mean differences (MDs) were calculated using a random-effects model. Review Manager 5.3 (The Cochrane Collaboration, Oxford, UK) was used for statistical analysis. Four studies, comprising two RCTs and two non-randomized cohort studies with 373 eyes of 372 patients, were included. The pooled analysis showed no significant difference in MH closure rates (OR 1.28; 95% confidence interval (CI): 0.48 to 3.43; P=0.62) and no difference concerning the incidence of adverse events (OR 0.97; 95% CI: 0.30-3.09; P=0.96). Leave-one-out sensitivity analysis excluding the study by Lauritzen et al. revealed a significant difference in anatomical closure, favoring the serum arm, and demonstrated a reduction in the level of heterogeneity. Our meta-analysis demonstrated no difference between groups in the pooled analysis of all studies. However, considering the quality assessment of one of the included studies, and observing the divergent result in sensitivity analysis following its exclusion, there are indications that might suggest the superiority of the serum in terms of the analyzed endpoints. This finding highlights the existing research gaps and the imperative need for additional high-quality randomized trials to further investigate this treatment.

Vitamin D Levels in Patients with Noninfectious Uveitis: A Systematic Review and Meta-Analysis.

PURPOSE: Vitamin D deficiency has been associated with higher rates of autoimmune disease, including noninfectious uveitis. This PRISMA-compliant review and meta-analysis aimed to analyze the correlation between noninfectious uveitis and vitamin D levels. METHODS: We searched PubMed, Embase, Cochrane, and Web of Science databases for studies, published in English, assessing vitamin D levels in patients diagnosed with noninfectious uveitis. The outcomes of interest were vitamin D deficiency, vitamin D mean level, vitamin D supplementation, and smoking rates. A subgroup analysis of inactive uveitis and active uveitis was performed. The heterogeneity was assessed with Cochrane Q-test and I2 statistics; p > 0.10 and I2 > 50% were considered significant for heterogeneity. Statistical analysis was conducted using Review Manager 5.3. RESULTS: 9 studies were included in the meta-analysis comprising a total of 10 711 patients, of whom 1,368 were diagnosed with noninfectious uveitis. Patients with noninfectious uveitis had worse results regarding vitamin D deficiency when compared with the control group (OR 0.58; CI 95% 0.44 to 0.77; p = 0.0002; I2 = 61%). Patients with inactive uveitis had better results towards vitamin D deficiency when compared with active uveitis (OR 5.00; CI 95% 2.84 to 8.81; p < 0.001; I2 = 0%). CONCLUSION: Our research supports the increasing evidence that associates vitamin D deficiency with noninfectious uveitis and its activity. Further investigation into the efficacy of vitamin D screening and supplementation in reducing the recurrence of uveitis is necessary.

Low-level red-light therapy for myopia control in children: A systematic review and meta-analysis.

INTRODUCTION: Low-Level Red-Light (LLRL) Therapy is a safe and natural way to promote healing and reduce inflammation in the body. When it comes to treating myopia in children, LLRL therapy is recent, and its efficacy and safety still are not clear. METHODS: A systematic review and meta-analysis of the literature for LLRL was conducted in accordance with the PRISMA guidelines on November 5, 2022. Databases, including PUBMED, Cochrane Library, Web of Science, and Embase were queried. A meta-analysis of random effects was conducted. Inclusion criteria included Randomized Controlled Trials (RCTs) or observational studies where LLRL therapy was used in children (3‒15 years old) with myopia. Exclusion criteria were studies with other ocular abnormalities. Efficacy was evaluated through the mean change in Axial Length (AL) and cycloplegic Spherical Equivalent Error (SER), while safety was evaluated by monitoring adverse effects. RESULTS: A total of 5 final studies were included (4 RCTs, and 1 observational), in which 685 total patients were analyzed. The mean age was 9.7 ± 0.66 years, with 48,2% female patients. The number of eyes in the LRLL arm is 714 and, in the control, arm is 656. LLRL showed better results in SER and AL mean change (OR = 0.58; 95% CI 0.33 to 0.83; p < 0.00001, and MD -0.33; 95% CI -0.52 to -0.13; p = 0.001, respectively), in comparison to the control group. There was no significant difference in adverse effects between groups (MD = 5.76; 95% CI 0.66 to 50.14; p = 0.11). CONCLUSION: LLRL therapy is a non-invasive, effective, and safe short-term treatment option; however, long-term evaluation, particularly in comparison to other therapies, requires additional investigation.

Large macular hole and autologous retinal transplantation: a systematic review and meta-analysis.

INTRODUCTION: Macular holes are breaks in the retinal tissue at the center of the macula, affecting central vision. The standard treatment involves vitrectomy with membrane peeling and gas tamponade. However, for larger or chronic holes, alternative techniques like autologous retinal graft have emerged. This meta-analysis evaluates the efficacy and safety of retinal transplantation in managing large macular holes. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. The study was prospectively registered in PROSPERO (CRD42024504801). We searched PubMed, Web of Science, Cochrane, and Embase databases for observational studies including individuals with large macular holes with or without retinal detachments and retinal transplantation as the main therapy. We used a random-effects model to compute the mean difference with 95% confidence intervals and performed statistical analysis using R software. RESULTS: We conducted a comprehensive analysis of 19 studies involving 322 patients diagnosed with various types of macular holes (MHs). These included cohorts with refractory MH, high myopia associated with MH, primary MH, and MH with retinal detachment (RD). The findings were promising, revealing an overall closure rate of 94% of cases (95% CI 88-98, I2 = 20%). Moreover, there was a significant improvement in postoperative visual acuity across all subgroups, averaging 0.45 (95% CI 0.33-0.58 ; I2 = 72%; p < 0.01) overall. However, complications occurred with an overall incidence rate of 15% (95% CI 7-25; I2 = 59%). CONCLUSION: ART for large MH shows promising results, including significant improvements in visual acuity and a high rate of MH closure with low complication risks overall and for subgroups.

Surgical management of retinal detachment and macular holes secondary to ocular toxoplasmosis: a systematic review and meta-analysis.

BACKGROUND: Toxoplasma gondii causes ocular toxoplasmosis (OT), involving inflammation, scarring, and retinal complications. The OT complications were retinal detachment (RD), and retinal breakage (RB). Surgical interventions like scleral buckling (SB) and vitrectomy are common. Limited understanding exists of the safety and efficacy of surgical management of RD/RB secondary to OT. Another complication is toxoplasmosis-related macular holes (tMH), with sparse evidence on surgical outcomes. This meta-analysis aims to clarify clinical characteristics, and surgical results, and enhance understanding of RD, RB, and MH secondary to OT. METHODS: PubMed, Cochrane, Embase and Web of Science database were queried for retrospective studies, case series and case reports that provided information on RD, RB and MH associated with OT and reported the outcomes of: (1) Retinal reattachment of RD/RB and tMH closure; (2) Best-corrected visual acuity (BCVA) improvement; and (3) Complications. Heterogeneity was examined with I2 statistics. A random-effects model was used for outcomes with high heterogeneity. Statistical analysis was performed using the software R (version 4.2.3, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Fourteen final studies, comprising a total of 96 patients were analyzed, 81 with RD or RB and 15 with tMH. Overall, surgical management was associated with several advantages: a high rate of retinal reattachment of RD/RB of 97% (95% Confidence Interval [CI] 92-100%; I2 = 0%), retinal reattachment of just RD of 96% (95% CI 89-100%; I2 = 30%) and tMH closure 97% (95% CI 87-100; I2 = 12%). There were significant differences in BCVA after surgeries in studies of RD/RB (MD 0.60; 95% CI 0.35-0.65; I2 = 20%) and MH (MD 0.67; 95% CI 0.50-0.84; I2 = 0%). The overall complication rate associated with surgical procedures in RD/RB secondary to OT was confirmed to be 25%. CONCLUSIONS: The systematic review and meta-analysis showed that the treatment approaches currently in use are effective, with a remarkable rate of retinal reattachment of RD/RB, tMH closure, and substantial improvements in visual acuity. More randomized, long-term studies on disease and surgical factors can provide valuable insights into their impact on anatomical and visual outcomes.

Combined Endoscopic Cyclophotocoagulation and Phacoemulsification Versus Phacoemulsification Alone in the Glaucoma Treatment: A Systematic Review and Meta-Analysis.

The complete safety and efficacy of endoscopic cyclophotocoagulation (ECP) remain unclear in the literature and, to our knowledge, there are no current meta-analyses on phaco-ECP versus phacoemulsification alone to date. Thus, we conducted a systematic review and meta-analysis comparing these two strategies through studies, assessing the effectiveness and safety of outcomes in a population with glaucoma. The protocol for this systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023482376). We systematically searched PubMed, Embase, and Web of Science from inception to December 2023. A random-effects model was used for all analyses due to heterogeneity. Review Manager 5.3 (Cochrane Centre, The Cochrane Collaboration, Denmark) was used for statistical analysis. Finally, nine studies were included in this comprehensive review and a total of 5389 eyes were analyzed in our study. In comparison to the ECP and phacoemulsification group, those receiving phacoemulsification alone showed better results in best-corrected visual acuity (MD 0.09; CI 95% 0.03 to 0.16; I²=0%), but worse outcomes in intraocular pressure (IOP) (MD -1.49; 95% CI -2.29 to -0.68; I²=29%) and use medications (MD -0.75; 95% CI -0.94 to -0.56; I²=0%) in the last visit. Complication rates, both general and serious, were significantly different between the groups, indicating the potential impact of combined procedures on patient outcomes. Thus, combining ECP with phacoemulsification for glaucoma treatment showed sustained IOP reduction and decreased medication dependence. However, higher complication rates suggest careful consideration of risks. More extensive research with larger trials and longer follow-ups is needed to validate findings and address limitations, providing valuable insights into this treatment approach.

Corneal Collagen Crosslinking for Ectasia After Refractive Surgery: A Systematic Review and Meta-Analysis.

Introduction: Corneal ectasia leads to progressive irregular corneal curvature and reduced visual acuity. Objective: To assess the safety and effectiveness of corneal collagen cross-linking (CXL) for managing corneal ectasia resulting from refractive laser surgery (RSL). Methods: A systematic review and meta-analysis were realized according to PRISMA guidelines. We searched PubMed, EMBASE, Cochrane, and Web of Science databases for studies on CXL in patients with ectasia after RLS. The outcomes of interest included visual acuity, refractive outcomes, topographic parameters (Kmax, index surface variance (ISV), index of Vertical Asymmetry (IVA), keratoconus index (KI), central keratoconus index (CKI), index of height asymmetry (IHA), index of height decentration (IHD) and Rmin (minimum sagittal curvature)), central corneal thickness, endothelial cell count, and possible adverse events. Statistical analysis was performed using the R software (version 4.2.3, R Foundation for Statistical Computing, Vienna, Austria). Results: 15 studies encompassing 421 patients (512 eyes) were included. The mean age was 32.03 ± 4.4 years. The pooled results showed a stable uncorrected visual acuity post-CXL, with a significant improvement in corrected distance visual acuity (SMD = 0.09; 95% CI: -0.07 to 0.26). The spherical equivalent decreased significantly (SMD = -0.09; 95% CI: -0.35, -0.02). The topographic parameter Kmax decreased significantly (SMD = 0.15; 95% CI:0.01 to 0.28); however, the other parameters, ISV, IVA, KI, CKI, IHA, IHD, and Rmin, did not change significantly. Central corneal thickness decreased significantly (SMD = 0.24; 95% CI:0.07 to 0.41), and the endothelial cell count remained stable The complications were rare. Conclusion: CXL is a safe and effective technique for managing corneal ectasia after RLS.

Novel pachymetric parameters based on corneal tomography for diagnosing keratoconus.

PURPOSE: To describe pachymetric progression indices (PPI) of the Pentacam HR (Oculus Optikgeräte GmbH) and the concept of relational thickness, and to test their accuracy for differentiating keratoconic and normal corneas compared with single-point thickness values. METHODS: One hundred thirteen individual eyes randomly selected from 113 normal patients and 44 eyes of 44 patients with keratoconus were studied using the Pentacam HR by acquiring central corneal thickness (CCT), thinnest point (TP), position of the TP and PPI at minimal (PPI Min) and maximal (PPI Max) meridians, and the average (PPI Ave) of all meridians. Relational thickness parameters were calculated as the ratios of TP and CCT and PPI values. Mann-Whitney U test assessed differences in groups for each variable. Receiver operating characteristic (ROC) curves were calculated for all variables and pairwise comparisons were performed. RESULTS: Statistically significant differences were noted between normal and keratoconic eyes for all parameters (P<.001), except for horizontal position of TP (P=.79). The best parameters, named Ambrósio's Relational Thickness (ART), were ART-Ave (TP/PPI Ave) and ART-Max (TP/PPI Max) with areas under the ROC curves of 0.987 and 0.983, respectively. The best cutoffs were 424 µm and 339 µm for ART-Ave and ART-Max, respectively. Pachymetric progression indices and ART had a greater area under the curve than TP and CCT (P<.001); TP (0.955) had a greater area under the curve than CCT (0.909; P=.002). CONCLUSIONS: Tomographic-derived pachymetric parameters were better able to differentiate normal and keratoconic corneas than single-point pachymetric measurements. Further studies are needed to evaluate the role of tomography in identifying early forms of ectasia as well as ectasia risk among LASIK candidates.

In vivo and in vitro toxicity evaluation of liposome-encapsulated sirolimus.

BACKGROUND: To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). METHODS: In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit's eyes following injection. RESULTS: Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p < 0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p = 1.0). The difference between groups 1 to 7 and group 8 (p < 0.0001) was significant. Histopathological changes were not found in any group. No activation of Müller cells was detected. CONCLUSION: A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.

Low-level red-light therapy for myopia control in children: A systematic review and meta-analysis

Abstract Introduction Low-Level Red-Light (LLRL) Therapy is a safe and natural way to promote healing and reduce inflammation in the body. When it comes to treating myopia in children, LLRL therapy is recent, and its efficacy and safety still are not clear. Methods A systematic review and meta-analysis of the literature for LLRL was conducted in accordance with the PRISMA guidelines on November 5, 2022. Databases, including PUBMED, Cochrane Library, Web of Science, and Embase were queried. A meta-analysis of random effects was conducted. Inclusion criteria included Randomized Controlled Trials (RCTs) or observational studies where LLRL therapy was used in children (3‒15 years old) with myopia. Exclusion criteria were studies with other ocular abnormalities. Efficacy was evaluated through the mean change in Axial Length (AL) and cycloplegic Spherical Equivalent Error (SER), while safety was evaluated by monitoring adverse effects. Results A total of 5 final studies were included (4 RCTs, and 1 observational), in which 685 total patients were analyzed. The mean age was 9.7 ± 0.66 years, with 48,2% female patients. The number of eyes in the LRLL arm is 714 and, in the control, arm is 656. LLRL showed better results in SER and AL mean change (OR = 0.58; 95% CI 0.33 to 0.83; p < 0.00001, and MD -0.33; 95% CI -0.52 to -0.13; p = 0.001, respectively), in comparison to the control group. There was no significant difference in adverse effects between groups (MD = 5.76; 95% CI 0.66 to 50.14; p = 0.11). Conclusion LLRL therapy is a non-invasive, effective, and safe short-term treatment option; however, long-term evaluation, particularly in comparison to other therapies, requires additional investigation.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AFTER PHOTOCOAGULATION OF TYPE 2 NEOVASCULARIZATION.

PURPOSE: To illustrate errors in the automated segmentation image analysis of optical coherence tomography angiography after laser photocoagulation therapy for Type 2 neovascularization. METHODS: This case report describes a patient with extrafoveal Type 2 neovascularization treated with argon laser photocoagulation evaluated before and after treatment by optical coherence tomography angiography. RESULTS: Disrupted retinal layers after laser photocoagulation therapy lead to segmentation errors. CONCLUSION: Images of optical coherence tomography angiography are prone to degradation by artifacts in cases in which there is disruption of the retinal layers. Clinicians must be aware of these errors because they can be misinterpreted as active Type 2 neovascularization. Improvement in optical coherence tomography angiography image analysis to minimize automated segmentation errors needs to be further explored.

Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is a progressive disease with multifactorial etiology. There is a need to identify clinical features that are harbingers of advanced disease. We evaluated morphologic features of the retina and choroid on optical coherence tomography (OCT) to determine if they predict progression to advanced disease. Methods: Progressors transitioned from early or intermediate AMD to advanced disease (n = 40 eyes), and were matched on baseline AMD grade and follow-up interval to nonprogressors who did not develop advanced AMD (n = 40 eyes). Features of the neurosensory retina, photoreceptors, retinal pigment epithelium (RPE), and choroid were evaluated. Logistic regression was used to evaluate univariate associations between features and progression to overall advanced AMD, geographic atrophy (GA), and neovascular disease (NV). Multivariate associations based on stepwise regression models were also assessed. Results: Ellipsoid zone disruption was associated with progression to overall advanced AMD and NV (odds ratios [ORs]: 17.9 and 30.6; P < 0.001), with a similar trend observed for GA. Drusenoid RPE detachment, RPE thickening, and retinal pigmentary hyperreflective material were significantly associated with higher risk of progression to advanced AMD (ORs: 5.0-8.5) and NV (ORs: 10.8-17.2). Pigmentary hyperreflective material was associated with progression to GA (OR: 7.5, P = 0.009). Total retinal thickness, pigmentary hyperreflective material, nascent GA features, and choroidal vessel abnormalities were independently associated with progression to advanced AMD in a multivariate stepwise model. Conclusions: Abnormalities in the photoreceptors, retinal thickness, RPE, and choroid were associated with higher risk of developing advanced AMD. These findings provide insights into disease progression, and may be helpful to identify earlier endpoints for clinical studies.