Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.

Glaucoma, a complex and multifactorial neurodegenerative disorder, is a leading cause of irreversible blindness worldwide. Despite significant advancements in our understanding of its pathogenesis and management, early diagnosis and effective treatment of glaucoma remain major clinical challenges. Epigenetic modifications, encompassing deoxyribonucleic acid (DNA) methylation, histone modifications, and non-coding RNAs, have emerged as critical regulators of gene expression and cellular processes. The aim of this comprehensive review focuses on the emerging field of epigenetics and its role in understanding the complex genetic and molecular mechanisms underlying glaucoma. The review will provide an overview of the pathophysiology of glaucoma, emphasizing the intricacies of intraocular pressure regulation, retinal ganglion cell dysfunction, and optic nerve damage. It explores how epigenetic modifications, such as DNA methylation and histone modifications, can influence gene expression, and how these mechanisms are implicated in glaucomatous neurodegeneration and contribute to glaucoma pathogenesis. The manuscript discusses evidence from both animal models and human studies, providing insights into the epigenetic alterations associated with glaucoma onset and progression. Additionally, it discusses the potential of using epigenetic modifications as diagnostic biomarkers and therapeutic targets for more personalized and targeted glaucoma treatment.

Biomarkers of Vitreous Cortex Remnants in Eyes With Primary Rhegmatogenous Retinal Detachment.

Purpose: The purpose of this study was to identify pre-operative biomarkers of vitreous cortex remnants (VCRs) in eyes with rhegmatogenous retinal detachment (RRD). Methods: Prospective case series of 103 eyes treated with pars plana vitrectomy (PPV) to repair RRD. Pre-operatively, optical coherence tomography (OCT) and B-scan ultrasonography (US) were used to study the vitreo-retinal interface and vitreous cortex status. If detected during PPV, VCRs were removed. Images acquired pre-operatively were compared with intra-operative findings and with postoperative OCT images taken at 1, 3, and 6 months of follow-up. Multivariate regression analyses were performed to determine associations between VCRs and pre-operative variables. Results: The presence of VCRs at the macula (mVCRs) and at the periphery (pVCRs), was ascertained intra-operatively in 57.3% and 53.4% of the eyes, respectively. Pre-operatively, a preretinal hyper-reflective layer (PHL) and a saw-toothed aspect of the retinal surface (SRS) were identified with OCT in 73.8% and 66% of the eyes, respectively. US sections showed a vitreous cortex running close and parallel to the detached retina upon static and kinetic examination (the "lining sign") in 52.4% of the cases. Multivariate regression analyses showed an association between PHL and SRS and intra-operative evidence of mVCRs (P = 0.003 and < 0.0001, respectively) and between SRS and "lining sign" and pVCRs (P = 0.0006 and 0.04, respectively). Conclusions: PHL and SRS on OCT and the "lining sign" on US appear to be useful pre-operative biomarkers of the intra-operative presence of VCRs. Translational Relevance: Preoperative identification of VCRs biomarkers may help to plan the operating strategy in eyes with RRD.

Ocular Tolerability of Bimatoprost 0.1 mg/mL Preservative-Free versus Bimatoprost 0.1 mg/mL with Benzalkonium Chloride or Bimatoprost 0.3 mg/mL Preservative-Free in Patients with Primary Open-Angle Glaucoma.

This study aimed to evaluate whether the therapeutic switch from a formulation of Bimatoprost 0.1 mg/mL with benzalkonium chloride (BAK) or Bimatoprost 0.3 mg/mL preservative-free to a formulation of Bimatoprost 0.1 mg/mL preservative-free could improve eye surface conditions in patients with glaucoma; intraocular pressure (IOP) was also evaluated. All patients meeting the inclusion criteria were eligible for the therapeutic switch to Bimatoprost 0.1 mg/mL preservative-free. At each check visit, enrolled patients underwent a break-up time (BUT) test, an ocular surface disease index (OSDI) test, and a three-point tonometric curve. A total of 40 patients were enrolled (23 were in therapy with Bimatoprost 0.1 mg/mL with BAK and 17 with Bimatoprost 0.3 mg/mL preservative-free). Significant differences of OSDI and BUT between Bimatoprost 0.1 mg/mL with BAK at baseline vs. Bimatoprost 0.1 mg/mL preservative-free at 14 and 28 days (p < 0.0001 and p = 0.0003, respectively) were recorded. Similarly, significant differences of OSDI and BUT between Bimatoprost 0.3 mg/mL preservative-free at baseline vs. Bimatoprost 0.1 mg/mL preservative-free at 14 and 28 days (p < 0.0001 for both) were found. Bimatoprost 0.1 mg/mL preservative-free has a better tolerability profile associated with non-therapeutical inferiority in the control of IOP compared to the other Bimatoprost formulations.

Effectiveness of oral probiotics supplementation in the treatment of adult small chalazion.

AIM: To define the possible beneficial impact of probiotics oral supplementation on patients affected by chalazion. METHODS: Prospective comparative pilot study on 20 adults suffering from chalazion randomly divided into two groups. The first group (n=10) received conservative treatment with lid hygiene, warm compression, and dexamethasone/tobramycin ointment for at least 20d. The second group (n=10), in addition to the conservative treatment, received a mixture of probiotic microorganisms of Streptococcus thermophilus ST10 (DSM 25246), Lactococcus lactis LLC02 (DSM 29536) and Lactobacillus delbrueckii (DSM 16606) once a day up to 3mo. Chalazia were classified according to their size into three groups: small (<2 mm), medium (≥2 to <4 mm), or large (≥4 mm). When conservative treatment with and without probiotics supplementation failed to resolve the lesion, invasive methods were used, intralesional steroid injection in medium size chalazion and surgical incision and curettage for the largest ones. RESULTS: Medical treatment with or without probiotics supplementation was effective only on the small size chalazia. There was a significant difference in the time taken for complete resolution of small size chalazia between the two groups in favor of the patients receiving probiotics (38.50±9.04d vs 21.00±7.00d, P=0.039). Medium and large size chalazia did not respond to medical treatment with or without probiotics supplementation over the follow-up period (3mo). The treatment did not induce any complications in both groups and no recurrence of chalaziosis was recorded in both groups. CONCLUSION: The considerable difference in time taken for complete resolution of small chalazia between the two groups in favor of the experimental one confirms the presence of a gut-eye axis.

Effect of COVID-19-related lockdown on ophthalmic practice in Italy: A report from 39 institutional centers.

BACKGROUND/OBJECTIVES: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). METHODS: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value <0.05 was considered significant. RESULTS: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65-0.80 and 0.61-0.75, respectively, p < 0.001 for both). CONCLUSION: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

Probiotic Supplementation Improved Acute Anterior Uveitis of 3-Year Duration: A Case Report.

BACKGROUND Uveitis is a clinical condition characterized by acute blurry vision related to an inflammation of the uvea. Gut microbiome dysbiosis can influence the prognosis of uveitis by inducing a loss of intestinal immune homeostasis leading to a lower activation threshold of the immune cells. This promotes a pro-inflammatory response resulting in reactivation of the disease. This is the case report of a 21-year-old woman with a 3-year history of acute anterior uveitis (AAU) of the right eye, who responded favorably to probiotic dietary supplementation. CASE REPORT A 21-year-old woman, previously unknown to our Ophthalmology Unit, presented with ocular pain and redness. Three years ago, she had been diagnosed with monolateral AAU in the right eye. Her medical and family histories were unremarkable. After a complete clinical evaluation, we decided to start a combination treatment protocol with continuous use of probiotics and the use of ocular steroids only during an exacerbation of the condition. To monitor the trend of the disease, she underwent a monthly clinical examination for the following year. During this period, we observed a decrease in ocular inflammation with a gain in the primary outcome (best-corrected visual acuity), and the steroids and atropine were discontinued for the following months. CONCLUSIONS This case report describes a patient with a 3-year history of AAU, who responded well to a combination treatment of dietary probiotic supplementation and steroids, demonstrating that probiotics can reduce recurrences of AAU.

Unintentional Retinal Displacement in Eyes Treated for Rhegmatogenous Retinal Detachment Complicated by Proliferative Vitreoretinopathy with Pars Plana Vitrectomy and Silicone Oil.

PURPOSE: To examine the clinical characteristics, outcomes, and rate of unintentional displacement in eyes treated for rhegmatogenous retinal detachment (RRD) with pars plana vitrectomy (PPV) and silicone oil (SO). METHODS: This retrospective observational study examined 50 eyes of 50 patients who underwent surgical repair for primary RRD complicated by proliferative vitreoretinopathy (PVR) by PPV and 1000-centistoke SO injection at a single institutional centre. The patients assumed a face-down posture immediately after surgery. Blue-fundus autofluorescence (B-FAF) pictures were obtained at 1 month after surgical procedures using a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). RESULTS: The primary success rate was obtained in 44 eyes (88%), on which the final analysis was conducted. Preoperative PVR was grade A in 7 eyes (15.9%), grade B in 28 eyes (63.6%), and grade C in 9 eyes (20.5%). The fovea was off and the detachment involved both the superior and inferior hemispheres of the retina in all cases. Breaks were located in the upper quadrants in 19 eyes (43.2%), in the lower quadrants in 12 eyes (27.3%), and in both upper and lower quadrants in 13 eyes (29.5%). The mean number of breaks was 3.4 ± 1.9. Intraoperative PFCL was used in 30 eyes (68.2%). Peeling of the epiretinal membrane/internal limiting membrane in the macula area was performed in 13 eyes (29.5%) during the first operation and carried out in all other eyes in occasion of SO removal. Preoperative BCVA was 2.1 ± 1.0 logMAR and improved to 0.8 ± 0.7 logMAR at the last follow-up (P < 0.0001). An upward unintentional retinal displacement was observed in 2 cases (4.5%). CONCLUSION: PPV and SO tamponade for complicated RRD are associated with good anatomical and functional outcomes and a very low rate of unintentional retinal displacement. Of the factors potentially implicated in favouring displacement that were studied, none were found significant.

Influence of gut microbiota on eye diseases: an overview.

The microbiota is a dynamic ecosystem that plays a major role in the host health. Numerous studies have reported that alterations in the intestinal microbiota (dysbiosis) may contribute to the pathogenesis of various common diseases such as diabetes, neuropsychiatric diseases, and cancer. However, emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor influencing the onset and progression of multiple ocular diseases, including uveitis, dry eye, macular degeneration, and glaucoma. Currently, supplementation with pre- and probiotics appears is the most feasible and cost-effective approach to restore the gut microbiota to a eubiotic state and prevent eye pathologies. In this review, we discuss the current knowledge on how gut microbiota may be linked to the pathogenesis of common eye diseases, providing therapeutic perspectives for future translational investigations within this promising research field.

Multimodal Imaging of Lamellar Macular Holes.

Evolution of imaging techniques has renewed interest in the diagnosis of lamellar macular hole (LMH) and greatly implemented the possibilities of gaining more detailed insights into its pathogenesis. Among noninvasive techniques, optical coherence tomography (OCT) is considered the primary examination modality to study LMHs, given its ability to image foveal structure and its widespread availability. OCT also allows to resolve the epiretinal materials associated with LMH, i.e., tractional epiretinal membranes (ERMs) and epiretinal proliferation (EP). En face OCT reconstructions are useful to confirm the foveal abnormalities shown by the eyes with LMH, whereas OCT angiography may reveal alterations of the size and shape of the foveal avascular zone and alterations of the density of the superficial and deep vascular plexuses. On slit-lamp biomicroscopy or fundus camera examination, LMH appears as a round or oval, reddish lesion at the center of the macula, slightly darker than the surrounding retina. The associated tractional ERM, causing wrinkling and glistening of the retinal surface, is usually readily appreciable, whereas EP is hardly apparent on biomicroscopy or fundus photography since the retina surface appears smooth. When imaged with blue fundus autofluorescence (B-FAF) imaging, LMHs are characterized by an increased autofluorescent signal, the intensity of which does not correlate with the thickness of the residual outer retinal tissue. Green reflectance and blue reflectance (BR) images clearly show the increased reflection and wrinkling of the retinal surface caused by tractional ERM associated with LMH. BR and multicolor imaging enable the visualization of EP associated with LMH in the form of a sharply demarcated dark area and in the form of a yellowish area surrounding the hole, respectively. Scarce data regarding invasive imaging techniques, such as fluorescein angiography, for the study of LMH are available in the literature. The aim of this review is to evaluate the contribution that each imaging modality can provide to study the morphologic characteristics of LMH.

Fluorescein Angiography Findings in Eyes With Lamellar Macular Hole and Epiretinal Membrane Foveoschisis.

Purpose: The purpose of this paper was to study fluorescein angiography (FA) findings in eyes with lamellar macular hole (LMH), and epiretinal membrane (ERM) foveoschisis. Methods: In this prospective, observational case series, 46 eyes of patients affected by either LMH or ERM foveoschisis were examined using optical coherence tomography (OCT) and FA. All patients underwent a comprehensive ophthalmological examination and a general workup to exclude uveitis. Main outcome measures were: presence of FA abnormalities, measurements of the areas of vascular leakage, and intensity of pixels in the vitreous. Results: Twenty-four (52.2%) eyes with LMH and 22 (47.8%) with ERM foveoschisis were studied. Overall, FA abnormalities were found in 20 (83.3%) eyes with LMH and 18 (81.8%) with ERM foveoschisis. The median areas of posterior pole and peripheral leakage were 7.52 vs. 1.07 mm2 (P = 0.03) and 21.8 vs. 3.74 mm2 (P = 0.02) in the LMH and ERM foveoschisis group, respectively. Disk hyperfluorescence was found in 8 and 4 eyes and perivascular leak in 10 and 4 eyes with LMH and ERM foveoschisis, respectively. OCT-derived measurements of vitreous intensity did not differ between the two groups, and the investigational workup for uveitis was negative in all patients. Conclusions: Discrete areas of central and peripheral leakage are commonly found in eyes with LMH and ERM foveoschisis, whereas perivascular leak and hyperfluorescence of the disc are less frequently observed. These findings suggest that breakdown of the retinal blood barrier, involving the posterior pole and the periphery, is frequently associated with these two vitreoretinal disorders.

Effects of the first month of lockdown for COVID-19 in Italy: A preliminary analysis on the eyecare system from six centers.

PURPOSE: To compare the number of eye surgical procedures performed in Italy during the first month of lockdown with those performed in the same period in 2019. METHODS: Review of the surgical procedures performed from 10 March to 9 April 2019 and from 10 March to 9 April 2020 (the first month of lockdown because of the COVID-19 outbreak) at six academic institutional centers of Italy. A distinction was made between urgent procedures: any trauma repairment, trabeculectomy/drainage implant for glaucoma, any operation for rhegmatogenous retinal detachment (RRD) repair, pars plana vitrectomy (PPV) for vitreous hemorrhage (VH), macular hole, or retained lens fragments; elective procedures: corneal transplant, phacoemulsification for cataract extraction, silicone oil removal, and PPV for epiretinal membrane; and intravitreal injections (either anti-vascular endothelial growth factor [VEGF] or dexamethasone) to treat exudative maculopathies. The main outcome measure was the rate of reduction in urgent and elective surgeries performed. RESULTS: Overall, 3624 and 844 surgical procedures were performed from 10 March to 9 April 2019 and from 10 March to 10 April 2020, respectively (-76.7% in 2020 compared to 2019, p < 0.0001). Urgent and elective surgical procedures and intravitreal injections of anti-VEGF drugs or dexamethasone reduced significantly in 2020 in comparison to 2019 (p < 0.0001 for urgent and elective surgeries and 0.01 for intravitreal injections). CONCLUSION: A significant reduction in the rate of urgent and elective surgeries and intravitreal injections was recorded during the first month of lockdown compared to the same period in 2019. With this analysis, the authors hope to provide some preliminary insights about the consequences of lockdown for the eyecare system in Italy.

Intestinal microbiome: a new target for chalaziosis treatment in children?

Intestinal dysbiosis (changes in the gut commensal microbiome) is related to several ophthalmic diseases. The aim of this study was to verify whether oral specific probiotics can alter the clinical course of chalaziosis and its recurrence. A prospective comparative pilot study involving 26 children suffering from chalaziosis was conducted. Children were randomly divided into two groups. The first group received medical treatment (lid hygiene, warm compression and dexamethasone/tobramycin ointment for at least 20 days), and the second group received medical treatment plus a daily supplementation of oral probiotics (≥ 1 × 10^9 live cells of Streptococcus thermophilus ST10 (DSM 25246), ≥ 1 × 10^9 live cells of Lactococcus lactis LCC02 (DSM 29536) and ≥ 1 × 10^9 live cells of Lactobacillus delbrueckii subsp. bulgaricus (DSM 16606) with maltodextrin as the bulking agent (Probiotical S.p.A., Novara, Italy). All patients were evaluated at 2-week intervals for 3 months. If the lesion had not disappeared or decreased in size to 1 mm or less in diameter at the time of subsequent visits, the same procedure was repeated for another 3-month cycle. There was a significant difference in the time taken for complete resolution of the chalazion between the two groups in favour of the children receiving the probiotics. The treatment was not associated with any significant complications in either group. Trial registration: The trial was registered at clinical trials.gov under NCT04322500 on 25/03/2020 ("retrospectively registered").Conclusions: Modification of the intestinal microbiome with specific probiotics can alter the clinical course of chalaziosis in children by re-establishing intestinal and immune homeostasis. Probiotic supplementation can increase the effectiveness of traditional therapies by prompting the complete resolution of chalaziosis in a shorter amount of time, in an easy and feasible way. What is Known: • The intestinal microbiome plays a crucial role in several inflammatory diseases of the eye and is considered a therapeutic target. • Probiotics play a role in the prevention and treatment of different conditions in children. What is New: • In children probiotic supplementation is safe and effective. • Probiotic supplementation reduced the time required for complete resolution of the chalazion.

Anti-inflammatory Effect of Curcumin, Homotaurine, and Vitamin D3 on Human Vitreous in Patients With Diabetic Retinopathy.

Purpose: To determine the levels of pro-inflammatory cytokines and soluble mediators (TNF-α, IL6, IL2, and PDGF-AB) in 28 vitreous biopsies taken from patients with proliferative diabetic retinopathy (PDR) and treated with increasing doses of curcumin (0. 5 and 1 µM), with or without homotaurine (100 µM) and vitamin D3 (50 nM). Materials and Methods: ELISA tests were performed on the supernatants from 28 vitreous biopsies that were incubated with bioactive molecules at 37°C for 20 h. The concentration of the soluble mediators was calculated from a calibration curve and expressed in pg/mL. Shapiro-Wilk test was used to verify the normality of distribution of the residuals. Continuous variables among groups were compared using the General Linear Model (GLM). Homoscedasticity was verified using Levene and Brown-Forsythe tests. Post-hoc analysis was also performed with the Tukey test. A p ≤ 0.05 was considered statistically significant. Results: The post-hoc analysis revealed statistically detectable changes in the concentrations of TNF-α, IL2, and PDGF-AB in response to the treatment with curcumin, homotaurine, and vitamin D3. Specifically, the p-values for between group comparisons are as follows: TNF-α: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.008, (curcumin 0.5 µM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0004, (curcumin 0.5 µM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.02, (curcumin 1 µM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.025, and (homotaurine 100 µM + vitamin D3 50 nM vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.009; IL2: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0023, and (curcumin 0.5 µM vs. curcumin 0.5 µM+ homotaurine 100 µM + vitamin D3 50 nM) p = 0.0028; PDGF-AB: (untreated vs. curcumin 0.5 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.04, (untreated vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.0006, (curcumin 0.5 µM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.006, and (homotaurine 100 µM + vitamin D3 50 nM vs. curcumin 1 µM + homotaurine 100 µM + vitamin D3 50 nM) p = 0.022. IL6 levels were not significantly affected by any treatment. Conclusions: Pro-inflammatory cytokines are associated with inflammation and angiogenesis, although there is a discrete variability in the doses of the mediators investigated among the different vitreous samples. Curcumin, homotaurine, and vitamin D3 individually have a slightly appreciable anti-inflammatory effect. However, when used in combination, these substances are able to modify the average levels of the soluble mediators of inflammation and retinal damage. Multi-target treatment may provide a therapeutic strategy for diabetic retinopathy in the future. Clinical Trial Registration : The trial was registered at clinical trials.gov as NCT04378972 on 06 May 2020 ("retrospectively registered") https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid = S0009UI8&selectaction = Edit&uid = U0003RKC&ts = 2&cx = dstm4o.

Clinical and Genetic Evaluation of a Cohort of Pediatric Patients with Severe Inherited Retinal Dystrophies.

We performed a clinical and genetic characterization of a pediatric cohort of patients with inherited retinal dystrophy (IRD) to identify the most suitable cases for gene therapy. The cohort comprised 43 patients, aged between 2 and 18 years, with severe isolated IRD at the time of presentation. The ophthalmological characterization also included assessment of the photoreceptor layer integrity in the macular region (ellipsoid zone (EZ) band). In parallel, we carried out a targeted, next-generation sequencing (NGS)-based analysis using a panel that covers over 150 genes with either an established or a candidate role in IRD pathogenesis. Based on the ophthalmological assessment, the cohort was composed of 24 Leber congenital amaurosis, 14 early onset retinitis pigmentosa, and 5 achromatopsia patients. We identified causative mutations in 58.1% of the cases. We also found novel genotype-phenotype correlations in patients harboring mutations in the CEP290 and CNGB3 genes. The EZ band was detectable in 40% of the analyzed cases, also in patients with genotypes usually associated with severe clinical manifestations. This study provides the first detailed clinical-genetic assessment of severe IRDs with infantile onset and lays the foundation of a standardized protocol for the selection of patients that are more likely to benefit from gene replacement therapeutic approaches.

Mutations in the PCYT1A gene are responsible for isolated forms of retinal dystrophy.

Mutations in the PCYT1A gene have been recently linked to two different phenotypes: one characterized by spondylometaphyseal dysplasia and cone-rod dystrophy (SMD-CRD) and the other by congenital lipodystrophy, severe fatty liver disease, and reduced HDL cholesterol without any retinal or skeletal involvement. Here, we identified, by next generation sequencing, sequence variants affecting function in the PCYT1A gene in three young patients with isolated retinal dystrophy from two different Italian families. A thorough clinical evaluation of the patients, with whole skeleton X-ray, metabolic assessment and liver ultrasound failed to reveal signs of skeletal dysplasia, metabolic and hepatic alterations. This is the first report showing that the PCYT1A gene can be responsible for isolated forms of retinal dystrophy, particularly without any skeletal involvement, thus further expanding the phenotypic spectrum induced by mutations in this gene.

Restoration of foveal thickness and architecture after macula-off retinal detachment repair.

PURPOSE: To investigate the foveal changes after repair of macula-off rhegmatogenous retinal detachment (RRD). METHODS: Prospective comparative case series. Twenty-four eyes of 24 patients with macula-off/fovea-on detachment (n = 9) and fovea-off detachment (n = 15) were studied. Serial optical coherence tomography (OCT) images taken at the same location were recorded at months 1, 3, 6, and 12 after operation. Fellow eyes were used as controls. RESULTS: No significant changes of the central foveal thickness (CFT) were recorded in the fovea-on group over the follow-up. From month 1 to month 12, CFT increased significantly in the fovea-off group (P < 0.00001). In this group, a significant increase of the Henle fiber and outer nuclear layer (HFL + ONL, P = 0.007), external limiting membrane (ELM)-ellipsoid zone (EZ; P = 0.03), and EZ-retinal pigment epithelium (RPE) thicknesses (P < 0.00001) was recorded. Significant restoration of the integrity of the ELM in the fovea-off group (P < 0.001) and of the EZ and cone interdigitation zone in the fovea-on group and the fovea-off group was observed (P = 0.02 and P < 0.001, and P = 0.002 and P < 0.001, respectively). Twelve months after operation the foveal bulge restored in 8 of 15 eyes of the fovea-off group. Multiple regression analysis showed that in the fovea-off group BCVA correlated with EZ-RPE thickness at months 1 and 12, whereas the improvement of BCVA during the 12 months follow-up correlated with the increase of ELM-RPE thickness. CONCLUSIONS: Optical coherence tomography scans taken serially at the same location showed a progressive increase of HNL+ONL, ELM-EZ, and EZ-RPE thicknesses and restoration of the integrity of outer retinal bands after repair of fovea-off RRD. The use of software able to rescan at exactly the same area is crucial to correctly follow and interpret the reconstitution of the retinal bands and to correlate them to BCVA recovery.

Corneal epithelial wound healing promoted by verbascoside-based liposomal eyedrops.

Different liposomal formulations were prepared to identify those capable of forming eyedrops for corneal diseases. Liposomes with neutral or slightly positive surface charge interact very well with the cornea. Then these formulations were loaded with verbascoside to heal a burn of corneal epithelium induced by alkali. The cornea surface affected involved in wound was monitored as a function of time. Experimental results were modeled by balance equation between the rate of healing, due to the flow of phenylpropanoid, and growth of the wound. The results indicate a latency time of only three hours and furthermore the corneal epithelium heals in 48 hours. Thus, the topical administration of verbascoside appears to reduce the action time of cells, as verified by histochemical and immunofluorescence assays.

Influence of retinal vessel printings on metamorphopsia and retinal architectural abnormalities in eyes with idiopathic macular epiretinal membrane.

PURPOSE: To investigate whether the presence of retinal vessel printings (RVPs) in eyes having idiopathic epiretinal membrane (ERM) is associated with a higher degree of metamorphopsia or with more prominent abnormalities in the retinal architecture compared with eyes not having RVPs. METHODS: A cross-sectional study of 36 eyes in 36 patients was conducted. The patients were divided into two groups (18 eyes per group) on the basis of the presence or absence of RVPs on fundus autofluorescence (FAF) imaging. Metamorphopsia was assessed using M-CHARTS. The optical coherence tomography (OCT) and FAF images were recorded using the Spectralis HRA+OCT. The macula was divided into 15 squares, and the areas between the displaced retinal vessels and the corresponding RVPs were calculated. RESULTS: Vertical, horizontal, and average metamorphopsia scores did not differ between the two groups. However, only two patients in the group with RVPs had an average metamorphopsia score of 0.6 or less versus nine patients in the group without RVPs (P = 0.029). There was no correlation between the area of displacement and vertical (P = 0.44), horizontal (P = 0.8), or average (P = 0.38) metamorphopsia scores. The eyes with RVPs manifested a higher degree of irregularity of the external limiting membrane (ELM) and the photoreceptor inner segment/outer segment (IS/OS) lines (P = 0.042 and P = 0.014, respectively). The presence of RVPs was the only independent variable associated with an average metamorphopsia score of 0.6 or higher. CONCLUSIONS: The presence of RVPs in eyes with idiopathic macular ERM is usually associated with an average metamorphopsia score of 0.6 or higher using M-CHARTS and with a higher degree of irregularity of the ELM and IS/OS lines at the fovea.