The 10q26 Risk Haplotype of Age-Related Macular Degeneration Aggravates Subretinal Inflammation by Impairing Monocyte Elimination.

A minor haplotype of the 10q26 locus conveys the strongest genetic risk for age-related macular degeneration (AMD). Here, we examined the mechanisms underlying this susceptibility. We found that monocytes from homozygous carriers of the 10q26 AMD-risk haplotype expressed high amounts of the serine peptidase HTRA1, and HTRA1 located to mononuclear phagocytes (MPs) in eyes of non-carriers with AMD. HTRA1 induced the persistence of monocytes in the subretinal space and exacerbated pathogenic inflammation by hydrolyzing thrombospondin 1 (TSP1), which separated the two CD47-binding sites within TSP1 that are necessary for efficient CD47 activation. This HTRA1-induced inhibition of CD47 signaling induced the expression of pro-inflammatory osteopontin (OPN). OPN expression increased in early monocyte-derived macrophages in 10q26 risk carriers. In models of subretinal inflammation and AMD, OPN deletion or pharmacological inhibition reversed HTRA1-induced pathogenic MP persistence. Our findings argue for the therapeutic potential of CD47 agonists and OPN inhibitors for the treatment of AMD.

Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation.

Variants of the CFH gene, encoding complement factor H (CFH), show strong association with age-related macular degeneration (AMD), a major cause of blindness. Here, we used murine models of AMD to examine the contribution of CFH to disease etiology. Cfh deletion protected the mice from the pathogenic subretinal accumulation of mononuclear phagocytes (MP) that characterize AMD and showed accelerated resolution of inflammation. MP persistence arose secondary to binding of CFH to CD11b, which obstructed the homeostatic elimination of MPs from the subretinal space mediated by thrombospsondin-1 (TSP-1) activation of CD47. The AMD-associated CFH(H402) variant markedly increased this inhibitory effect on microglial cells, supporting a causal link to disease etiology. This mechanism is not restricted to the eye, as similar results were observed in a model of acute sterile peritonitis. Pharmacological activation of CD47 accelerated resolution of both subretinal and peritoneal inflammation, with implications for the treatment of chronic inflammatory disease.

Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.

PURPOSE: To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. DESIGN: Randomized, open-label, multicenter superiority study. PARTICIPANTS: Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium. METHODS: Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 µg], and 20% sulfur hexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal tPA [50 µg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. MAIN OUTCOME MEASURES: The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. RESULTS: Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference ß, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group. CONCLUSIONS: Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intravitreal Injection of Bevacizumab for the Prevention of Postoperative Proliferative Vitreoretinopathy in High-Risk Patients Selected by Laser Flare Photometry.

INTRODUCTION: To evaluate the effect of an intravitreal injection of bevacizumab at the time of rhegmatogenous retinal detachment (RRD) surgery, on postoperative proliferative vitreoretinopathy (PVR) in high-risk patients selected by laser flare photometry. METHODS: This single-center observational retrospective cohort study included 137 consecutive patients who underwent pars plana vitrectomy and gas tamponade for primary RRD with increased aqueous flare between July 2016 and June 2021. From June 2019, an intravitreal injection of bevacizumab was administered as an adjunct to RRD repair. Patients who underwent surgery before this time and who did not receive intravitreal bevacizumab served as controls. The main outcome was the rate of retinal redetachment due to PVR. RESULTS: The median flare value was 22.0 (16.5-36.5) pc/ms in the control group and 28.2 (19.7-41.0) pc/ms in the bevacizumab group (p = 0.063). Eyes treated with bevacizumab were more likely to have macula-off RRD (p = 0.003), grade B PVR (p = 0.038), and worse visual acuity (p = 0.004) than controls. The rate of PVR redetachment was significantly lower in the bevacizumab group (11.1%) than in the control (30.1%) (p = 0.012). This difference was more pronounced after adjusting for potential confounding factors (p = 0.005); the risk of developing PVR was 4.5-fold higher in controls (95% CI, 1.6-12.8). After adjustment, the final median visual acuity was also significantly higher in eyes treated with bevacizumab (p = 0.025). CONCLUSION: This pilot study provides preliminary evidence that bevacizumab may reduce the risk of PVR-related recurrent RRD and improve visual outcomes in high-risk patients selected by laser flare photometry.

Ocular manifestations in patients with inborn errors of intracellular cobalamin metabolism: a systematic review.

Inherited disorders of cobalamin (cbl) metabolism (cblA-J) result in accumulation of methylmalonic acid (MMA) and/or homocystinuria (HCU). Clinical presentation includes ophthalmological manifestations related to retina, optic nerve and posterior visual alterations, mainly reported in cblC and sporadically in other cbl inborn errors.We searched MEDLINE EMBASE and Cochrane Library, and analyzed articles reporting ocular manifestations in cbl inborn errors. Out of 166 studies a total of 52 studies reporting 163 cbl and 24 mut cases were included. Ocular manifestations were found in all cbl defects except for cblB and cblD-MMA; cblC was the most frequent disorder affecting 137 (84.0%) patients. The c.271dupA was the most common pathogenic variant, accounting for 70/105 (66.7%) cases. One hundred and thirty-seven out of 154 (88.9%) patients presented with early-onset disease (0-12 months). Nystagmus and strabismus were observed in all groups with the exception of MMA patients while maculopathy and peripheral retinal degeneration were almost exclusively found in MMA-HCU patients. Optic nerve damage ranging from mild temporal disc pallor to complete atrophy was prevalent in MMA-HCU.and MMA groups. Nystagmus was frequent in early-onset patients. Retinal and macular degeneration worsened despite early treatment and stabilized systemic function in these patients. The functional prognosis remains poor with final visual acuity < 20/200 in 55.6% (25/45) of cases. In conclusion, the spectrum of eye disease in Cbl patients depends on metabolic severity and age of onset. The development of visual manifestations over time despite early metabolic treatment point out the need for specific innovative therapies.

Effect of Duration of Silicone Oil Tamponade on Retinal Structure after Rhegmatogenous Retinal Detachment Surgery.

PURPOSE: The aim of the study was to investigate the effect of tamponade duration on retinal changes induced by silicone oil (SO) in patients who underwent successful rhegmatogenous retinal detachment (RRD) surgery. METHODS: Retrospective comparative case series of 68 patients who underwent SO tamponade for RRD. Patients were divided into 2 groups based on timing of SO removal: <6 months (group 1, n = 34) versus ≥6 months (group 2, n = 34). The main outcome measure was the change in central macular, inner, and outer retinal layer thickness (CMT, IRLT, and ORLT) before and after SO removal (SOR). RESULTS: The median tamponade duration was 4 [Clin Ophthalmol. 2016;10:471-6, Zhonghua Yan Ke Za Zhi. 1997 Jan;33(1):39-41] months in group 1 and 8 [Arch Ophthalmol. 1994 Jun;112(6):778-85, Retina. 2004 Dec;24(6):871-7] months in group 2 (p < 0.001). The mean CMT significantly increased from 245.3 ± 22.2 µm and 238.8 ± 41.6 µm under SO to 281.3 ± 60.2 µm and 259.0 ± 43.5 µm after SOR in group 1 (p = 0.009) and in group 2 (p = 0.007), respectively. Automated segmentation measurement revealed a significant increase in mean IRLT (p = 0.014 and p = 0.013) but no change in mean ORLT (p = 0.080 and p = 0.257) in both groups. After adjustment, there was no difference between the 2 groups in terms of mean final CMT, IRLT, and ORLT and mean retinal thickness changes after SOR. There was also no correlation between the tamponade duration and macular microstructural changes or visual recovery. CONCLUSION: SO tamponade causes a thinning of all retinal layers, mainly affecting the inner retinal layer. However, these changes resolved following SO extraction and were not affected by longer tamponade duration.

Hypoxia Inhibits Subretinal Inflammation Resolution Thrombospondin-1 Dependently.

Hypoxia is potentially one of the essential triggers in the pathogenesis of wet age-related macular degeneration (wetAMD), characterized by choroidal neovascularization (CNV) which is driven by the accumulation of subretinal mononuclear phagocytes (MP) that include monocyte-derived cells. Here we show that systemic hypoxia (10% O2) increased subretinal MP infiltration and inhibited inflammation resolution after laser-induced subretinal injury in vivo. Accordingly, hypoxic (2% O2) human monocytes (Mo) resisted elimination by RPE cells in co-culture. In Mos from hypoxic mice, Thrombospondin 1 mRNA (Thbs1) was most downregulated compared to normoxic animals and hypoxia repressed Thbs-1 expression in human monocytes in vitro. Hypoxic ambient air inhibited MP clearance during the resolution phase of laser-injury in wildtype animals, but had no effect on the exaggerated subretinal MP infiltration observed in normoxic Thbs1-/--mice. Recombinant Thrombospondin 1 protein (TSP-1) completely reversed the pathogenic effect of hypoxia in Thbs1-/--mice, and accelerated inflammation resolution and inhibited CNV in wildtype mice. Together, our results demonstrate that systemic hypoxia disturbs TSP-1-dependent subretinal immune suppression and promotes pathogenic subretinal inflammation and can be therapeutically countered by local recombinant TSP-1.

Ophthalmologic manifestations in patients with antiphospholipid antibodies: Beware of iatrogenic complications.

BACKGROUND: Antiphospholipid syndrome (APS) is characterized by several clinical manifestations such as venous and arterial thrombosis associated with persistent antiphospholipid antibodies (aPL). Several studies confirmed that retinal vein occlusion was the most common APS ocular manifestation. The purpose of this study was to identify ophthalmologic manifestations in a homogeneous cohort of well-defined persistently aPL-positive patients and to determine variables associated with these manifestations. METHODS: APL-positive patients were selected from two research programs. All ophthalmologic manifestations including those related to APS were recorded. RESULTS: A total of 117 patients were included and 10 of them had APS-related ophthalmologic manifestations (glaucoma, hydroxychloroquine-related maculopathy, anterior acute uveitis, anterior ischemic optic neuropathy). Systemic Lupus Erythematosus (SLE) (OR = 3.4[95%CI; 0.9-12.7), corticosteroids (OR = 9.0 [95%CI; 2.2-37.7]) and aPL-related nephropathy (OR = 7.1 [95%CI; 1.7-30.0]) were significatively associated with the risk of APS-related ophthalmologic manifestations. CONCLUSION: Most of ocular manifestations in this study were iatrogenic related to corticosteroids or hydroxychloroquine. Patients with SLE, small vessel thrombosis in general, or with aPL-related nephropathy in particular, seemed at higher risk to develop APS-related ophthalmologic manifestations thus deserving adequate monitoring.

OUTCOMES OF COMBINED PHACOEMULSIFICATION AND PARS PLANA VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: A Comparative Study.

PURPOSE: To evaluate and to compare the anatomical and functional results of phacovitrectomy and pars plana vitrectomy (PPV) alone for phakic rhegmatogenous retinal detachment. METHODS: Retrospective, comparative case series of 266 phakic eyes that underwent either combined phacovitrectomy or PPV alone for primary retinal detachment. The primary anatomical success rate, the final best-corrected visual acuity, and the refractive outcomes were analyzed. RESULTS: One hundred and twenty-seven eyes were included in the combined group and 139 in the PPV group. The primary anatomical success rate was 84.3% in the combined group and 89.2% in the PPV group (P = 0.311). One hundred and nine (78.4%) eyes of the PPV group required cataract removal for visual rehabilitation during the follow-up period. There was no significant difference between the two groups in terms of the mean final best-corrected visual acuity (P = 0.185) and mean visual changes (P = 0.470). Overall, combined cataract extraction resulted in a significant myopic shift compared with delayed cataract surgery (P = 0.047). CONCLUSION: Combined phacoemulsification and PPV is a safe and effective procedure to treat retinal detachment. The anatomical and functional results were comparable with those obtained with PPV and delayed cataract surgery. However, the refractive outcomes were less favorable and shifted toward myopia, especially in macula-off cases.

Insulin inhibits inflammation-induced cone death in retinal detachment.

BACKGROUND: Rhegmatogenous retinal detachment (RD) involving the macula is a major cause of visual impairment despite high surgical success rate, mainly because of cone death. RD causes the infiltration of activated immune cells, but it is not clear whether and how infiltrating inflammatory cells contribute to cone cell loss. METHODS: Vitreous samples from patients with RD and from control patients with macular hole were analyzed to characterize the inflammatory response to RD. A mouse model of RD and retinal explants culture were then used to explore the mechanisms leading to cone death. RESULTS: Analysis of vitreous samples confirms that RD induces a marked inflammatory response with increased cytokine and chemokine expression in humans, which is closely mimicked by experimental murine RD. In this model, we corroborate that myeloid cells and T-lymphocytes contribute to cone loss, as the inhibition of their accumulation by Thrombospondin 1 (TSP1) increased cone survival. Using monocyte/retinal co-cultures and TSP1 treatment in RD, we demonstrate that immune cell infiltration downregulates rod-derived cone viability factor (RdCVF), which physiologically regulates glucose uptake in cones. Insulin and the insulin sensitizers rosiglitazone and metformin prevent in part the RD-induced cone loss in vivo, despite the persistence of inflammation CONCLUSION: Our results describe a new mechanism by which inflammation induces cone death in RD, likely through cone starvation due to the downregulation of RdCVF that could be reversed by insulin. Therapeutic inhibition of inflammation and stimulation of glucose availability in cones by insulin signaling might prevent RD-associated cone death until the RD can be surgically repaired and improve visual outcome after RD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03318588.

Lebecetin, a C-type lectin, inhibits choroidal and retinal neovascularization.

Angiogenesis is a cause of visual impairment and blindness in the wet form of age-related macular degeneration and in ischemic retinopathies. Current therapies include use of anti-VEGF agents to reduce choroidal neovascularization (CNV) and edema. These treatments are effective in most cases, but spontaneous or acquired resistance to anti-VEGF and possible adverse effects of long-term VEGF inhibition in the retina and choroid highlight a need for additional alternative therapies. Integrins αvß3 and αvß5, which regulate endothelial cell proliferation and stabilization, have been implicated in ocular angiogenesis. Lebecetin (LCT) is a 30-kDa heterodimeric C-type lectin that is isolated from Macrovipera lebetina venom and interacts with α5ß1- and αv-containing integrins. We previously showed that LCT inhibits human brain microvascular endothelial cell adhesion, migration, proliferation, and tubulogenesis. To evaluate the inhibitory effect of LCT on ocular angiogenesis, we cultured aortic and choroidal explants in the presence of LCT and analyzed the effect of LCT on CNV in the mouse CNV model and on retinal neovascularization in the oxygen-induced retinopathy model. Our data demonstrate that a single injection of LCT efficiently reduced CNV and retinal neovascularization in these models.-Montassar, F., Darche, M., Blaizot, A., Augustin, S., Conart, J.-B., Millet, A., Elayeb, M., Sahel, J.-A., Réaux-Le Goazigo, A., Sennlaub, F., Marrakchi, N., Messadi, E., Guillonneau, X. Lebecetin, a C-type lectin, inhibits choroidal and retinal neovascularization.

Visual Outcomes of Pars Plana Vitrectomy with Epiretinal Membrane Peeling in Patients with Asteroid Hyalosis: A Matched Cohort Study.

BACKGROUND: The study aimed to evaluate outcomes of epiretinal membrane (ERM) peeling in patients with asteroid hyalosis (AH) and to compare them with those from controls without AH. METHODS: This is a retrospective matched cohort study of 1,104 consecutive patients who underwent surgery for ERM between January 2004 and February 2014. Patients with AH were included in the study group and were matched for preoperative visual acuity, age, gender, date of surgery, and axial length with control patients without AH selected from the same cohort. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) on optical coherence tomography were measured at baseline and postoperatively with a minimum follow-up period of 12 months. RESULTS: A total of 44 patients were included in the AH group and 44 in the control group. The mean initial BCVA was 0.53 ± 0.21 LogMAR for the AH group vs. 0.49 ± 0.20 LogMAR for the control group, and the mean initial CMT was 419 ± 74 vs. 423 ± 75 µm, respectively. During the follow-up, no significant difference was found regarding the final BCVA at 6 months (0.23 ± 0.14 vs. 0.24 ± 0.17) LogMAR (p = 0.87) and 12 months (0.16 ± 0.09 vs. 0.17 ± 0.12) LogMAR (p = 0.92), despite a tendency toward slower visual recovery for the AH group at 1 month, with a mean BCVA of 0.36 ± 0.12 vs. 0.28 ± 0.18 LogMAR (p = 0.08). No difference was found regarding the progression of CMT at 1.6 and 12 months with a mean CMT of 396 ± 47 vs. 378 ± 55 µm (p = 0.39), 356 ± 39 vs. 365 ± 41 µm (p = 0.48), and 349 ± 68 vs. 352 ± 53 µm (p = 0.87), respectively. CONCLUSION: Vitrectomy with ERM peeling in patients with AH was beneficial and showed similar functional and anatomical outcomes in both groups. AH does not seem to affect visual improvement or the complication rate after ERM peeling. Therefore, the indications for vitrectomy in case of ERM should not be prompted by the presence of AH.

Outcomes of macular hole surgery with short-duration positioning in highly myopic eyes: a case-control study.

PURPOSE: To evaluate the outcomes of macular hole (MH) surgery with 3-day prone positioning in highly myopic eyes and to compare them with those from non-highly myopic eyes. DESIGN: Retrospective nested case-control study from a cohort of 496 consecutive patients (496 eyes) who underwent surgery for MH. PARTICIPANTS: Forty-seven highly myopic eyes (with axial length >26 mm) were included in the study group and were matched for MH size and duration of symptoms with 47 non-highly myopic control eyes selected from the same cohort. METHODS: All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and 17% hexafluoroethane gas filling. Patients then were advised to maintain strict face-down positioning for 3 days only and to avoid the supine position during the night for a minimum of 1 week. MAIN OUTCOME MEASURES: The MH closure rate, the relationship between axial length and closure rate, the best-corrected visual acuity (BCVA), and the surgical complications were analyzed. RESULTS: The mean axial length was 28.5±2.2 mm in highly myopic eyes and 23.3±1.1 mm in controls (P < 0.001). Closure of the MH was achieved in 39 of 47 eyes (83%) in the study group and in 45 of 47 eyes (95.7%) in the control group (P = 0.045). Anatomic outcomes tended to decrease when axial length increased (P = 0.066). Mean BCVA improved in both groups (0.41±0.39 logarithm of the minimal angle of resolution [logMAR] vs. 0.68±0.34 logMAR) but was significantly lower in highly myopic eyes (P < 0.001). Retinal detachment occurred in 8.5% of highly myopic patients versus 2.1% of controls, but the difference was not significant. CONCLUSIONS: Macular hole surgery with 3-day postoperative positioning in highly myopic eyes resulted in satisfactory anatomic and functional outcomes. However, the MH closure rate and mean improvement of visual acuity were less favorable than those in control eyes. Longer axial length may increase the risk of anatomic failure.

Dissociated Optic Nerve Fiber Layer Appearance after Macular Hole Surgery: A Randomized Controlled Trial Comparing the Temporal Inverted Internal Limiting Membrane Flap Technique with Conventional Peeling.

PURPOSE: To evaluate the effect of the temporal inverted internal limiting membrane (ILM) flap technique compared with that of conventional ILM peeling on the extent of the dissociated optic nerve fiber layer (DONFL) and retinal sensitivity in patients undergoing macular hole (MH) surgery. DESIGN: Single-center, prospective, open-label, randomized controlled clinical trial. PARTICIPANTS: Patients requiring vitrectomy for MHs sized > 250 µm. METHODS: Patients were randomly assigned (1:1) to 1 of the following 2 groups: (1) the control group undergoing standard ILM peeling and (2) the experimental group (flap group) undergoing the temporal inverted ILM flap technique. MAIN OUTCOME MEASURES: The primary outcome measure was the total DONFL score at 3 months after surgery. Important secondary outcomes were microperimetry results, primary MH closure rate, external limiting membrane (ELM) and ellipsoid zone (EZ) recovery rates, and best-corrected visual acuity (BCVA). RESULTS: Sixty-five patients were recruited between February 2018 and July 2020; primary outcome data were available for 60 patients. The median DONFL score was 7.0 (3.0-12.5) in the control group and 5.0 (1.5-8.5) in the flap group at 3 months after surgery (P = 0.145). The focal depressions characteristic of the DONFL were limited to the temporal side of the fovea in the flap group, whereas they were found all around the fovea in the control group on spectral-domain OCT images. The MH closure rate (P = 1), EZ and ELM recovery rates (P = 0.252), and BCVA (P = 0.450) were similar between the 2 groups. The 3-month overall median retinal sensitivity (MRS) (P = 0.142) and MRS improvement (P = 0.916) in the control group were comparable with those observed in the flap group. In addition, there was no significant difference between the 2 techniques when considering the temporal area (P = 0.105) or the nasal area (P = 0.468). CONCLUSIONS: The temporal inverted ILM flap technique reduced the extent of the DONFL by preserving the nasal part of the fovea. However, the overall DONFL score was similar between the 2 techniques. In addition, the MRS and BCVA did not differ from those obtained after complete ILM peeling. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy of the DRL orthokeratology lens in slowing axial elongation in French children.

Background: This study aims to assess and compare the impact of Orthokeratology Double Reservoir Lens (DRL) versus Single Vision Lenses (SVL) on axial elongation and anterior chamber biometric parameters in myopic children over a 6- and 12-month treatment period in France. Methods: A retrospective study involving 48 patients aged 7 to 17 years, who underwent either orthokeratology treatment or single-vision spectacle correction, was conducted. Changes in refractive error, axial length, and anterior chamber depth were examined. Results: Twenty-five patients comprised the Orthokeratology (OK) group, while twenty-three were in the control group (single-vision spectacle group). Significant increases in mean axial length were observed over time in both the control (0.12 ± 0.13 mm and 0.20 ± 0.17 mm after 6 and 12 months, respectively; F (2,28.9) = 27.68, p < 0.001) and OK groups (0.02 ± 0.07 mm and 0.06 ± 0.13 mm after 6 and 12 months, respectively; F (2,29.1) = 5.30, p = 0.023). No statistically significant differences in axial length were found between male and female children (p > 0.620). Age-specific analysis revealed no significant axial elongation after 12 months in the 14-17 years group in the OK group. Anterior biometric data analysis at 6 and 12 months showed statistical significance only for the DRL group. Conclusion: Orthokeratology resulted in an 86 and 70% reduction in axial elongation after 6 and 12 months of lens wear, respectively, compared to the single-vision spectacles group. Myopia progression was more pronounced in younger children, underscoring the importance of initiating myopia control strategies at early ages.

A transgenic mice model of retinopathy of cblG-type inherited disorder of one-carbon metabolism highlights epigenome-wide alterations related to cone photoreceptor cells development and retinal metabolism.

BACKGROUND: MTR gene encodes the cytoplasmic enzyme methionine synthase, which plays a pivotal role in the methionine cycle of one-carbon metabolism. This cycle holds a significant importance in generating S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the respective universal methyl donor and end-product of epigenetic transmethylation reactions. cblG type of inherited disorders of vitamin B12 metabolism due to mutations in MTR gene exhibits a wide spectrum of symptoms, including a retinopathy unresponsive to conventional therapies. METHODS: To unveil the underlying epigenetic pathological mechanisms, we conducted a comprehensive study of epigenomic-wide alterations of DNA methylation by NGS of bisulfited retinal DNA in an original murine model with conditional Mtr deletion in retinal tissue. Our focus was on postnatal day 21, a critical developmental juncture for ocular structure refinement and functional maturation. RESULTS: We observed delayed eye opening and impaired visual acuity and alterations in the one-carbon metabolomic profile, with a notable dramatic decline in SAM/SAH ratio predicted to impair DNA methylation. This metabolic disruption led to epigenome-wide changes in genes involved in eye development, synaptic plasticity, and retinoid metabolism, including promoter hypermethylation of Rarα, a regulator of Lrat expression. Consistently, we observed a decline in cone photoreceptor cells and reduced expression of Lrat, Rpe65, and Rdh5, three pivotal genes of eye retinoid metabolism. CONCLUSION: We introduced an original in vivo model for studying cblG retinopathy, which highlighted the pivotal role of altered DNA methylation in eye development, cone differentiation, and retinoid metabolism. This model can be used for preclinical studies of novel therapeutic targets.

Prevalence and predictive factors for posterior vitreous attachment in eyes undergoing epiretinal membrane surgery.

BACKGROUND: To report the prevalence of posterior vitreous attachment (PVA) in patients with idiopathic epiretinal membrane (iERM) and to determine associated preoperative predictive factors. METHODS: Retrospective observational case series of 408 eyes who underwent surgery for iERM without vitreomacular traction. The status of the posterior hyaloid was assessed intraoperatively. Predictive factors were analysed using univariate and multivariate logistic regression. We also evaluated the effect of PVA on the anatomical and functional outcomes of surgery. RESULTS: Eighty-two (20.1%) eyes were found to have an undetached posterior hyaloid during vitrectomy. In multivariate analysis, axial length (AL) and lens status were strongly associated with the posterior vitreous status (p = 0.031 and p = 0.048). The odds of having a PVA decreased by a factor 0.81 per mm of AL (95% CI, 0.66-1.00). Phakic eyes had a 2.88-fold increased risk of exhibiting PVA compared to those with previous cataract extraction (95% CI, 1.10-7.52). The presence of PVA did not have any effect on postoperative anatomical and functional outcomes. In contrast, we found that eyes with shorter axial length, low preoperative visual acuity and disruption of the ellipsoid zone exhibited worse visual recovery (p = 0.006, p < 0.001 and p = 0.037). CONCLUSION: PVA was observed in 20.1% of eyes undergoing vitrectomy for iERM. Shorter AL and phakic status were strong predictive factors of PVA in those eyes. However, the morphological features and the surgical prognosis of iERMs with PVA did not differ from those with posterior vitreous detachment.

Association of Microvasculature Changes with Visual Outcomes after Successful Retinal Detachment Surgery.

PURPOSE: To evaluate macular microvascular changes and their correlation with visual outcomes after rhegmatogenous retinal detachment (RRD) surgery. DESIGN: Retrospective case series. PARTICIPANTS: The study included 74 eyes successfully operated for RRD. METHODS: The foveal avascular zone area in the superficial capillary plexus, the vessel density (VD) in the superficial capillary plexus, vessel density deep capillary plexus (VD DCP), and choriocapillary plexus were evaluated using octangiography at 1 and 6 months postoperatively. The fellow eyes were used as controls for comparison. MAIN OUTCOME MEASURES: The correlation between octangiography parameters and postoperative best-corrected visual acuity (BCVA) was assessed using a hybrid linear mixed model. We also analyzed the relationship between octangiography parameters and the integrity of the external limiting membrane (ELM) and ellipsoid zone (EZ) of photoreceptors. RESULTS: The median VD DCP was significantly decreased in RRD eyes at 1 month (P = 0.019), but gradually improved over time to reach the value of the fellow eyes at 6 months (P = 1). There was no significant difference between the 2 groups in median foveal avascular zone area, superficial capillary plexus, and choriocapillary plexus (P = 0.579, P = 0.618, P = 0.068 and P = 0.819, P = 1, and P = 1, respectively) at both 1 and 6 months postoperatively. Postoperative BCVA was positively correlated with VD DCP (P = 0.009) in multivariate analysis. Eyes with low 1-month VD DCP tended to have worse final BCVA (P = 0.067). There was no correlation between VD DCP and ELM and/or EZ integrity at both 1 (P = 0.156) and 6 months postoperatively (P = 0.161). Eyes with intact ELM and EZ at 6 months, however, had significantly higher 1-month VD DCP than those with disrupted ELM and/or EZ (P = 0.027). CONCLUSION: The VD DCP was affected in RRD eyes as well as strongly associated with postoperative BCVA and the restoration of photoreceptor layers. It might thus serve as a predictor for visual recovery following successful RRD surgery.