Compensation of inner retina to early-stage photoreceptor degeneration in a RhoP23H/+ mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal disorder characterized by the degeneration of photoreceptors. RhoP23H/+ mice, which carry a Pro23His mutation in the RHODOPSIN (Rho) gene, are one of the most studied animal models for RP. However, except for the photoreceptors, other retinal neural cells have not been fully investigated in this model. Here, we record the temporal changes of the retina by optical coherence tomography (OCT) imaging of the RhoP23H/+ mice, from early to mid-phase of retinal degeneration. Based on thickness analysis, we identified a natural retinal thickness adaption in wild-type mice during early adulthood and observed morphological compensation of the inner retina layer to photoreceptor degeneration in the RhoP23H/+ mice, primarily on the inner nuclear layer (INL). RhoP23H/+ mice findings were further validated via: histology showing the negative correlation of INL and ONL thicknesses; as well as electroretinogram (ERG) showing an increased b-wave to a-wave ratio. These results unravel the sequential morphologic events in this model and suggest a better understanding of retinal degeneration of RP for future studies.

Arylalkylamine N-acetyltransferase (AANAT): Blue light induction, nuclear translocation, and potential role in the survival of chicken retina neuronal cells.

In vertebrates, arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) is the time-keeping and key regulatory enzyme in melatonin (Mel) biosynthesis. AANAT is present in the pineal gland, retina, and other regions where it is controlled by light, cyclic adenosine monophosphate (cAMP) levels, and the molecular clock. AANAT converts serotonin to N-acetyl serotonin (NAS) and the last enzyme in the pathway, hydroxy-o-methyltransferase (HIOMT), forms Mel by NAS methylation. We have previously shown that AANAT is expressed in chicken retinal ganglion cells (RGCs) during daytime at the level of mRNA and enzyme activity. Here we investigated the presence of AANAT protein and mRNA throughout development in the chicken embryonic retina as well as AANAT expression, phosphorylation, and its sub-cellular localization in primary cultures of retinal neurons from E10 embryonic retinas exposed to blue light (BL) and controls kept in the dark (D). From embryonic days 7-10 (E7-10) AANAT mRNA and protein were visualized mainly concentrated in the forming ganglion cell layer (GCL), while from E17 through postnatal days, expression was detectable all through the different retinal cell layers. At postnatal day 10 (PN10) when animals were subjected to a 12:12 h LD cycle, AANAT was mainly expressed in the GCL and inner nuclear layer cells at noon (Zeitgeber Time (ZT 6)) and in the photoreceptor cell layer at night (ZT 21). Primary cultures of retinal neurons exhibited an induction of AANAT protein when cells were exposed to BL for 1 h as compared with D controls. After BL exposure, AANAT showed a significant change in intracellular localization from the cytoplasm to the nucleus in the BL condition, remaining in the nucleus 1-2 h in the D after BL stimulation. BL induction of nuclear AANAT was substantially inhibited when cultures were treated with the protein synthesis inhibitor cycloheximide (CHD). Furthermore, the phosphorylated form of the enzyme (pAANAT) increased after BL in nuclear fractions obtained from primary cultures as compared with D controls. Finally, the knockdown of AANAT by sh-RNA in primary cultures affected cell viability regardless of the light condition. AANAT knockdown also affected the redox balance, sh-AANAT treated cultures showing higher levels of reactive oxygen species (ROS) than in the sh-control. Our results support the idea that AANAT is a BL-sensing enzyme in the inner retina of diurnal vertebrates, undergoing phosphorylation and nuclear importation in response to BL stimulation. Moreover, it can be inferred that AANAT plays a novel role in nuclear function, cell viability, and, likely, through redox balance regulation.

A randomised controlled trial evaluating internal limiting membrane peeling forceps in macular hole surgery.

PURPOSE: To assess study design and a range of anatomical and functional changes after internal limiting membrane (ILM) peeling using forceps developed for atraumatic ILM pick-up compared to standard forceps. METHODS: We conducted a masked proof-of concept randomised controlled trial (RCT) on 65 patients who underwent ILM peeling for idiopathic full-thickness macular hole (FTMH) using etched-tip forceps (etched-tip group, 33 eyes) compared to standard ILM forceps (smooth-tip group, 32 eyes). Patients were assessed preoperatively, 3 weeks, 3 and 6 months postoperatively. RESULTS: The primary closure rate was 95.4%. There was no statistically significant difference between the groups in terms of final visual acuity (66.9 vs 70.9 ETDRS letters, p = 0.13), difference of visual field mean deviation (1.32 vs 1.14 decibels), and number of eyes with pick-up-related retinal haemorrhages (16% vs 16%, p = 0.96), swelling of arcuate nerve fibre layer lesions (63% vs 55%, p = 0.54), number of dissociated optic nerve fibre layer lesions (31.4 vs 41.0, p = 0.16), nor inner retina defects (37% vs 22%, p = 0.17). Similar changes in inner retinal volumes were detected in all 9 sectors of an ETDRS grid except for a trend (p = 0.06) towards a lower reduction in the inferior inner sector in the etched-tip group. CONCLUSIONS: The study was successfully completed with masking maintained and a low risk of bias. Multiple endpoints relating to ILM peeling were assessed, and estimates were provided that can be used for future studies. Although the study was not powered to assess any specific endpoint, the anatomical and functional outcomes assessed did not significantly differ.

The thickness of the outer retina in the macula and circumpapillary area in patients with unilateral advanced glaucoma.

PURPOSE: To compare outer macular and retinal thickness in the circumpapillary area in unilateral advanced glaucomatous eyes to the normal or mild glaucomatous fellow eyes. METHODS: Seventy-eight eyes of 39 patients with unilateral advanced glaucoma (mean deviation (MD) worse than -12.00 dB based on visual field 24-2) were included in this cross-sectional study as the cases. The healthy or mild glaucomatous fellow eyes were enrolled as the control group. All eyes underwent optical coherence tomography of the macula and circumpapillary retina by Topcon DRI Triton (Topcon, Tokyo, Japan). Ganglion cell layer 2+ was considered as the inner retina. Total retinal thickness minus the thickness of the inner retina was considered as the outer retina. Comparison between groups was done by paired-sample sign test. The correlation between structural and functional parameters was evaluated by a partial correlation coefficient. RESULTS: Seventeen (43.6%), 15 (38.5%), and 7 (17.9%) patients had pseudoexfoliation, primary angle-closure, and primary open-angle glaucoma, respectively. The mean age was 62.69 ± 12.00 years. Thirty-three (84.6%) patients were male. The outer retinal thickness in the circumpapillary area was higher in temporal, superior, and inferior quadrants (p < 0.05). The outer macula in different parafoveal and perifoveal quadrants was also thicker (p < 0.05). Average outer parafoveal thickness in the case group had a significant negative correlation with MD (r = -0.339; p = 0.035). CONCLUSION: Advanced glaucomatous eyes had a thicker outer retina in the macula and circumpapillary area. There was a significant negative correlation between outer perifoveal thickness and MD.

Angulation of the inner nuclear layer as an indicator of the severity of macular pseudohole.

PURPOSE: To investigate foveal morphologic parameters related to visual acuity and the stages classified in this study reflect the severity of the macular pseudohole (MPH). METHODS: Seventy-eight eyes of 78 consecutive patients diagnosed with MPH were studied. Quantitative optical coherence tomography (OCT) parameters including central foveal thickness, parafoveal thickness, parafoveal inner and outer retinal thickness (PIRT and PORT), pseudohole depth, pseudohole diameter, and inner nuclear layer (INL) angulation were measured and the morphologic features of the inner retina (disorganization of retinal inner layers (DRIL)) and the photoreceptor layer (external limiting membrane (ELM), ellipsoid zone (EZ), interdigitation zone (IZ), and cotton ball sign) were determined. Associations between OCT parameters and best-corrected visual acuity (BCVA) were analyzed. Based on the location of the inner margin of INL, all patients were divided into three stages and the mean comparison between the three stages was analyzed. RESULTS: PIRT (r = 0.6489; p < 0.0001) and pseudohole depth (r = 0.5266; p < 0.0001) had a statistically significant correlation with BCVA. Statistically significant visual acuity differences were found in eyes with DRIL (p < 0.001) and IZ disruption (p = 0.018), but not in ELM disruption (p = 0.916), EZ disruption (p = 0.581), and cotton ball sign (p = 0.075). According to the univariate and multivariate regression analyses, PIRT was associated with BCVA in both univariate (p < 0.001) and multivariate (p = 0.002) regression analyses. Defect diameters of both ELM (p = 0.025) and IZ (p = 0.006) were associated with BCVA in univariate regression analysis, but not in multivariate regression analysis. INL angulation and the ratio of the IZ disruption was significantly different in the three groups. Stage 3 (95.8%) had significantly higher disrupted IZ ratio than stage 1 (40%) and stage 2 (65.5%). The BCVA of stages 1, 2, and 3 were identified as 0.06 ± 0.07 (20/23 Snellen equivalent), 0.23 ± 0.17 (20/34 Snellen equivalent), and 0.48 ± 0.23 (20/60 Snellen equivalent), respectively, and the differences in BCVA between the three groups were significant (p < 0.0001). CONCLUSION: The parameters related to visual acuity were PIRT, pseudohole depth, DRIL, and IZ. The stage classification proposed in this study included morphologic changes of the inner retina and photoreceptor layer and is likely to be clinically useful for showing the severity of the MPH.

Investigation of tissue cysts in the retina in a mouse model of ocular toxoplasmosis: distribution and interaction with glial cells.

The conversion of tachyzoites into bradyzoites is a way for Toxoplasma gondii to establish a chronic and asymptomatic infection and achieve lifelong persistence in the host. The bradyzoites form tissue cysts in the retina, but not much is known about the horizontal distribution of the cysts or their interactions with glial cells in the retina. A chronic ocular toxoplasmosis model was induced by per oral administration of T. gondii Me49 strain cysts to BALB/c mice. Two months after the infection, retinas were flat-mounted and immunostained to detect cysts, ganglion cells, Müller cells, astrocytes, and microglial cells, followed by observation under fluorescence and confocal microscope. The horizontal distribution showed a rather clustered pattern, but the clusters were not restricted to certain location of the retina. Axial distribution was confined to the inner retina, mostly in ganglion cell layer or the inner plexiform layer. Both ganglion cells, a type of retinal neurons, and Müller cells, predominant retinal glial cells, could harbor cysts. The cysts were spatially separated from astrocytes, the most abundant glial cells in the ganglion cell layer, while close spatial distribution of microglial cells was observed in two thirds of retinal cysts. In this study, we demonstrated that the retinal cysts were not evenly distributed horizontally and were confined to the inner retina axially. Both neurons and one type of glial cells could harbor cysts, and topographic analysis of other glial cells suggests role of microglial cells in chronic ocular toxoplasmosis.

Caffeine exposure alters adenosine system and neurochemical markers during retinal development.

Evidence points to beneficial properties of caffeine in the adult central nervous system, but teratogenic effects have also been reported. Caffeine exerts most of its effects by antagonizing adenosine receptors, especially A1 and A2A subtypes. In this study, we evaluated the role of caffeine on the expression of components of the adenosinergic system in the developing avian retina and the impact of caffeine exposure upon specific markers for classical neurotransmitter systems. Caffeine exposure (5-30 mg/kg by in ovo injection) to 14-day-old chick embryos increased the expression of A1 receptors and concomitantly decreased A2A adenosine receptors expression after 48 h. Accordingly, caffeine (30 mg/kg) increased [(3) H]-8-cyclopentyl-1,3-dipropylxanthine (A1 antagonist) binding and reduced [(3) H]-ZM241385 (A2A antagonist) binding. The caffeine time-response curve demonstrated a reduction in A1 receptors 6 h after injection, but an increase after 18 and 24 h. In contrast, caffeine exposure increased the expression of A2A receptors from 18 and 24 h. Kinetic assays of [(3) H]-S-(4-nitrobenzyl)-6-thioinosine binding to the equilibrative adenosine transporter ENT1 revealed an increase in Bmax with no changes in Kd , an effect accompanied by an increase in adenosine uptake. Immunohistochemical analysis showed a decrease in retinal content of tyrosine hydroxylase, calbindin and choline acetyltransferase, but not Brn3a, after 48 h of caffeine injection. Furthermore, retinas exposed to caffeine had increased levels of phosphorylated extracellular signal-regulated kinase and cAMP-response element binding protein. Overall, we show an in vivo regulation of the adenosine system, extracellular signal-regulated kinase and cAMP-response element binding protein function and protein expression of specific neurotransmitter systems by caffeine in the developing retina. The beneficial or maleficent effects of caffeine have been demonstrated by the work of different studies. It is known that during animal development, caffeine can exert harmful effects, impairing the correct formation of CNS structures. In this study, we demonstrated cellular and tissue effects of caffeine's administration on developing chick embryo retinas. Those effects include modulation of adenosine receptors (A1 , A2 ) content, increasing in cAMP response element-binding protein (pCREB) and extracellular signal-regulated kinase phosphorylation (pERK), augment of adenosine equilibrative transporter content/activity, and a reduction of some specific cell subpopulations. ENT1, Equilibrative nucleoside transporter 1.

Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype.

The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms.

Differential regulation of feeding rhythms through a multiple-photoreceptor system in an avian model of blindness.

All organisms have evolved photodetection systems to synchronize their physiology and behavior with the external light-dark (LD) cycles. In nonmammalian vertebrates, the retina, the pineal organ, and the deep brain can be photoreceptive. Inner retinal photoreceptors transmit photic information to the brain and regulate diverse nonvisual tasks. We previously reported that even after preventing extraretinal photoreception, blind GUCY1* chickens lacking functional visual photoreceptors could perceive light that modulates physiology and behavior. Here we investigated the contribution of different photoreceptive system components (retinal/pineal and deep brain photoreceptors) to the photic entrainment of feeding rhythms. Wild-type (WT) and GUCY1* birds with head occlusion to avoid extraocular light detection synchronized their feeding rhythms to a LD cycle with light >12 lux, whereas at lower intensities blind birds free-ran with a period of >24 h. When released to constant light, both WT and blind chickens became arrhythmic; however, after head occlusion, GUCY1* birds free-ran with a 24.5-h period. In enucleated birds, brain illumination synchronized feeding rhythms, but in pinealectomized birds only responses to high-intensity light (≥800 lux) were observed, revealing functional deep brain photoreceptors. In chickens, a multiple photoreceptive system, including retinal and extraretinal photoreceptors, differentially contributes to the synchronization of circadian feeding behavior.

Optimized feline vitrectomy technique for therapeutic stem cell delivery to the inner retina.

OBJECTIVE: To describe an optimized surgical technique for feline vitrectomy which reduces bleeding and aids posterior gel clearance in order to facilitate stem cell delivery to the inner retina using cellular scaffolds. PROCEDURES: Three-port pars plana vitrectomies were performed in six-specific pathogen-free domestic cats using an optimized surgical technique to improve access and minimize severe intraoperative bleeding. RESULTS: The surgical procedure was successfully completed in all six animals. Lens sparing vitrectomy resulted in peripheral lens touch in one of three animals but without cataract formation. Transient bleeding from sclerotomies, which was readily controlled, was seen in two of the six animals. No cases of vitreous hemorrhage, severe postoperative inflammation, retinal detachment, or endophthalmitis were observed during postoperative follow-up. CONCLUSIONS: Three-port pars plana vitrectomy can be performed successfully in the cat in a safe and controlled manner when the appropriate precautions are taken to minimize the risk of developing intraoperative hemorrhage. This technique may facilitate the use of feline models of inner retinal degeneration for the development of stem cell transplantation techniques using cellular scaffolds.

Inner retinal thickness in Stargardt disease.

PURPOSE: To analyze the alterations at the level of the inner retina in patients affected by Stargardt disease (STGD1). METHODS: Cross-sectional investigation involving STGD1 patients with genetically confirmed diagnosis, who underwent optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), and microperimetry. RESULTS: Overall, 31 patients (62 eyes) with genetically confirmed STGD1 were included in the study. Mean inner retinal thickness, vessel density of plexa, and retinal sensitivity resulted significantly reduced in STGD patients, compared with healthy controls (p < 0.05), both in the outer and in the inner ETDRS rings. Overall, 43% of eyes revealed an inner retinal thinning, whereas 21% and 35% showed a thicker or within normal range inner retina. CONCLUSIONS: Inner retina is irregularly altered in STGD1, showing variable quantitative alterations as detected on OCT. Inner retinal status might represent a useful biomarker to better characterize STGD1 and to ascertain the effects of new treatment approaches.

Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma.

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.

Retinal OCT findings in acute central retinal artery occlusion of varying severity at different disease stages - a retrospective, observational study.

PURPOSE: To study the optical coherence tomography (OCT) changes in eyes with acute central retinal artery occlusion (CRAO) of different severity and at different disease stages. METHODS: The study included acute CRAO cases of < 7 days duration, imaged on OCT at various time points. Based on the OCT findings at presentation, cases were classified into three severity groups: mild, moderate, and severe. OCT scans were evaluated and classified into four-time intervals based on symptom duration. RESULTS: There were 39 eyes from 38 patients with acute CRAO who underwent 96 OCT scans. At presentation, the study had 11, 16, and 12 cases of mild, moderate, and severe CRAO, respectively. Middle retinal layer opacification was more common in mild CRAO cases, which caused inner retinal layer thinning over time. Moderate CRAO cases had total inner retinal layer opacification, which resulted in retinal thinning over time. Prominent middle limiting membrane (p-MLM) sign was seen in mild and moderate CRAO eyes while were not visualised in severe CRAO. This sign gradually faded out over time. Other OCT findings in higher grades of CRAO included inner retinal fluid, neurosensory detachment, internal limiting membrane detachment, hyperreflective foci, and posterior vitreous opacities. Regardless of the CRAO grade, the final end-point seen was inner retinal layer thinning over time. CONCLUSION: OCT in CRAO is a useful for determining the severity of retinal ischemia, disease stage, tissue damage mechanism, and final visual outcome. More prospective studies analysing a larger number of cases at fixed time points will be required in the future. TRIAL REGISTRATION: Trial Registration Number: Not applicable.

Longitudinal Structure-Function Evaluation in a Patient with CDHR1-Associated Retinal Dystrophy: Progressive Visual Function Loss with Retinal Remodeling.

BACKGROUND: Retinal dystrophies related to damaging variants in the cadherin-related family member 1 (CDHR1) gene are rare and phenotypically heterogeneous. Here, we report a longitudinal (three-year) structure-function evaluation of a patient with a CDHR1-related retinal dystrophy. METHODS: A 14-year-old girl was evaluated between 2019 and 2022. An ophthalmological assessment, including color vision, perimetry, electroretinography, and multimodal imaging of the retina, was performed periodically every six months. Next-generation sequencing disclosed two likely pathogenic/pathogenic variants in the CDHR1 gene, in compound heterozygosity, confirmed by segregation analysis. RESULTS: At first examination, the patient showed a cone-rod pattern retinal dystrophy. Over follow-up, there was a decline of visual acuity and perimetric sensitivity (by ≥0.3 and 0.6 log units, respectively). Visual loss was associated with a progressive increase in inner retinal thickness (by 30%). Outer retina showed no detectable changes over the follow-up. CONCLUSIONS: The results indicate that, in this patient with a CDHR1-related cone-rod dystrophy, the progression to severe visual loss was paralleled by a progressive inner retinal thickening, likely a reflection of remodeling. Inner retinal changes over time may be functionally relevant in view of the therapeutic attempts based on gene therapy or stem cells to mitigate photoreceptor loss.

Middle-Inner Macular Layers Dysfunction in a Case of Stellate Foveomacular Retinoschisis Detected by Abnormal Multifocal Photopic Negative Response Recordings.

We describe the macular morpho-functional assessment of a 65-year-old man affected by stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR), studied by visual field, SD-OCT, autofluorescence, full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG) and multifocal Photopic Negative Response (mfPhNR) recordings. The typical presentation consists of the foveal appearance of radial cartwheel pattern for the splitting of the retinal layers at the level of the Henle fiber layer (HFL) and the outer plexiform layer (OPL), perfectly seen by Spectral Domain-Optical Coherence Tomography (SD-OCT). Despite a normal function of the outer retina of the peripheral and central retina evaluated by ffERG and mfERG respectively, we observed a reduced function of the retinal elements involved in the retinoschisis by recording mfPhNR that assesses mainly inner retina function (retinal ganglion cells and their axons). Therefore, it is likely that the observed impaired mfPhNR responses reflect the signaling defects derived from the delaminated middle retina and transmitted to the innermost retinal layers.

Inner Retinal Layer Thickness Alterations in Early Age Related Macular Degeneration in Eyes with Subretinal Drusenoid Deposits or Conventional Drusen.

The purpose of this study was to evaluate central and parafoveal inner retinal layer thickness in patients with subretinal drusenoid deposits (SDD) or conventional drusen (CD). Participants underwent comprehensive ophthalmoscopic examination. Evidence of SDD or CD was evaluated with near infrared reflectance and spectral domain optical coherence tomography. Quantification of subfoveal lesions was made through a qualitative analysis of vertical and horizontal SD-OCT scans centered on the fovea. Inner retinal layer macular thickness measurements were obtained for central circles with 1, 3, and 5 mm diameter. Continuous variables were compared by the analysis of covariance (ANCOVA) with post-hoc Tukey HSD correction for multiple comparison analysis. Fifty-five patients were included in the study; 18 eyes with SDD alone, 19 eyes with CD alone, and 18 eyes of healthy age-matched subjects. Eight eyes with SDD (44%) and 13 eyes with CD (68%) had subfoveal lesions. There was significant reduction in the inner retinal layer thickness in the central 1mm area and in the superior 3 mm area in the SDD and CD group compared to controls. In conclusion the inner retinal layer is thinner in the central macula and in the superior parafovea in eyes.

Optic pit-like maculopathy in a patient without any detectable disc anomalies.

Macular schisis is the splitting of the inner retinal layers at macula, with or without associated detachment. The acquired form of macular schisis is frequently associated with optic disc pit maculopathy, although it could be accompanied by several conditions such as tractional maculopathies, cystoid macular edema, veno-occlusive disease, and shaken baby syndrome. However, a small number of cases of retinoschisis without optic disc pit have been reported elsewhere. Here, we present a patient with acquired macular schisis without high myopia and optic disc abnormality in funduscopic examination and imaging. Macular optical coherence tomography of her left eye revealed schisis of the inner and outer retinal layers and subretinal fluid and choroidal thickness of 426 µm (pachychoroid). Although the optic disc of this patient appeared normal, the probable presumption is that small junctions existed between the macular neuroretinal tissue and the vitreous cavity. Further studies are required to survey the other probable mechanisms of retinoschisis without optic pit with more subjects.

Diabetic macular edema with neuroretinal detachment: OCT and OCT-angiography biomarkers of treatment response to anti-VEGF and steroids.

PURPOSE: To assess and compare early changes in neuroinflammatory and vascular parameters in diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND) after treatment with intravitreal dexamethasone (DEX-I) and ranibizumab (IVR). METHODS: Thirty-three eyes (33 patients) with treatment naïve DME with SND were retrospectively evaluated at baseline and 2 months after DEX-I (15 eyes) and 1 month after 3 monthly IVR injections (18 eyes). Inclusion criteria were: complete eye examination, good quality OCT and OCT-A images. OCT parameters included: central macular thickness (CMT); number of hyper-reflective retinal spots (HRS) in inner, outer (IR, OR) and full retina; choroidal thickness (CT), extent of disorganization of inner retinal layers (DRIL), outer retina integrity (OR). On OCT-A: foveal avascular zone (FAZ) parameters in the superficial capillary plexus (SCP); cysts area and perfusion density (PD) in SCP and deep capillary plexus (DCP) and flow voids (FV) in choriocapillaris. FAZ was analyzed using ImageJ, perfusion parameters and FV using MATLAB. RESULTS: BCVA increased equally after both treatments (13.0 ± 10.0 ETDRS letters, p < 0.0001). There was a similar decrease (p < 0.05) in: height of SND, cysts area at SCP, central and mean CT, increase in FAZ perimeter and OR integrity, after both treatments. A greater decrease in DEX-I versus IVR group was found in: CMT (- 38.7% vs. - 22.2%, p = 0.012), HRS number in IR (- 29.2% vs. - 14.0%, p = 0.05) and full retina (- 24.7% vs. - 8.0%, p = 0.03), DRIL extension (- 62.0% vs. - 24%, p = 0.008), cysts area at DCP (- 68.7% vs. - 26.1%, p = 0.03), FAZ-CI (- 19.1% vs. - 8.3%, p = 0.02), PD at DCP (- 27.5% vs. + 4.9%, p = 0.02). FV did not change. CONCLUSIONS: More pronounced changes in specific inflammatory parameters in the inner retina are documented after steroid versus anti-VEGF treatment. These include reduction in HRS number, DRIL extension, CMT, cysts area at DCP. These data may help in further study of noninvasive imaging biomarkers for better evaluation of treatment response.

Glaucomatous Maculopathy: Thickness Differences on Inner and Outer Macular Layers between Ocular Hypertension and Early Primary Open-Angle Glaucoma Using 8 × 8 Posterior Pole Algorithm of SD-OCT.

The purpose of this study was to compare the thickness of all inner and outer macular layers between ocular hypertension (OHT) and early primary open-angle glaucoma (POAG) using spectral domain optical coherence tomography (SD-OCT) 8 × 8 posterior pole algorithm (8 × 8 PPA). Fifty-seven eyes of 57 OHT individuals and fifty-seven eyes of 57 early POAG patients were included. The thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform and nuclear layer, photoreceptor layer (PRL) and retinal pigment epithelium were obtained in 64 cells for each macular layer and mean thickness of superior and inferior hemispheres was also calculated. Thinning of superior and inferior hemisphere mean thickness in mRNFL, GCL and IPL and thickening of superior and inferior hemisphere mean thickness in PRL and inferior hemisphere in INL were found in early GPAA group. Otherwise, heatmaps representing cell-to-cell comparisons showed thinning patterns in inner retinal layers (except for INL) and thickening patterns in outer retinal layers in GPAA group. We found that 8 × 8 PPA not only allows the detection of significant thinning patterns in inner retinal layers, but also thickening patterns in outer retinal layers when comparing early POAG eyes to OHT eyes.

Disorganization of the retinal inner layers as a prognostic factor in eyes with central retinal artery occlusion.

AIM: To evaluate baseline foveal disorganisation of retinal inner layers (DRIL) as a prognostic factor in eyes with central retinal artery occlusion (CRAO). METHODS: Twenty-eight CRAO patients who were followed-up between 2010 and 2016 were retrospectively investigated. Demographic characteristics and detailed ophthalmological examination findings of all patients were recorded. Macular thicknesses (MTs) from 5 separate spots and DRIL were measured with spectral-domain optic coherence tomography (SD-OCT). Correlations between DRIL score and logMAR converted visual acuity (VA), change in VA, patient reference time (RT), number of hyperbaric oxygen therapy (HBOT) sessions, MT and MT change were investigated. RESULTS: There was a positive correlation between the DRIL score and the final VA (r=0.787) and a negative correlation with the change in VA (r=-0.763). The RT and MT were closely related to the DRIL score. A negative correlation was found between the number of HBOT sessions and the DRIL score (r=-0.341). CONCLUSION: The DRIL score is a parameter assessed by SD-OCT, which can provide us reliable information regarding the prognosis of visual functions and response to the treatment for CRAO patients at acute phase.