Thinning Of Inner Retinal Layers Research Articles

Noninvasive Ophthalmic Imaging Measures Retinal Degeneration and Vision Deficits in Ndufs4-/- Mouse Model of Mitochondrial Complex I Deficiency.

PurposeTo characterize postnatal ocular pathology in a Ndufs4−/− mouse model of complex I deficiency using noninvasive retinal imaging and visual testing.Methods Ndufs4−/− mice and wild-type (WT) littermates were analyzed at 3, 5, and 7 weeks postnatal. Retinal morphology was visualized by optical coherence tomography (OCT). OCT images were analyzed for changes in retinal thickness and reflectivity profiles. Visual function was assessed by electroretinogram (ERG) and optomotor reflex (OMR).Results Ndufs4−/− animals have normal OCT morphology at weaning and develop inner plexiform layer atrophy over weeks 5 to 7. Outer retinal layers show hyporeflectivity of the external limiting membrane (ELM) and photoreceptor ellipsoid zone (EZ). Retinal function is impaired at 3 weeks, with profound deficits in b-wave, a-wave, and oscillatory potential amplitudes. The b-wave and oscillatory potential implicit times are delayed, but the a-wave implicit time is unaffected. Ndufs4−/− animals have normal OMR at 3 weeks and present with increasing acuity and contrast OMR deficits at 5 and 7 weeks. Physiological thinning of inner retinal layers, attenuation of ELM reflectivity, and attenuation of ERG b- and a-wave amplitudes occur in WT C57BL/6 littermates between weeks 3 and 7.ConclusionsNoninvasive ocular imaging captures early-onset retinal degeneration in Ndufs4−/− mice and is a tractable approach for investigating retinal pathology subsequent to complex I deficiency.Translational RelevanceOphthalmic imaging captures clinically relevant measures of retinal disease in a fast-progressing mouse model of complex I deficiency consistent with human Leigh syndrome.

Genetic inhibition of collapsin response mediator protein-2 phosphorylation ameliorates retinal ganglion cell death in normal-tension glaucoma models.

Glaucoma is a neurodegenerative disorder caused by the death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is a cause of glaucoma. However, glaucoma often develops with normal IOP and is known as normal-tension glaucoma (NTG). Glutamate neurotoxicity is considered as one of the significant causes of NTG, resulting in excessive stimulation of retinal neurons via the N-methyl-D-aspartate (NMDA) receptors. The present study examined the phosphorylation of collapsin response mediator protein-2 (CRMP2), a protein that is abundantly expressed in neurons and involved in their development. In two mouse models, NMDA-injection and glutamate/aspartate transporter (GLAST) mutant, CRMP2 phosphorylation at the cyclin-dependent kinase-5 (Cdk5) site was elevated in RGCs. We confirmed that the decrease in the number of RGCs and thickness of the inner retinal layer (IRL) could be suppressed after NMDA administration in CRMP2KI/KI mice with genetically inhibited CRMP2 phosphorylation. Next, we investigated GLAST heterozygotes (GLAST+/-) with CRMP2KI/KI (GLAST+/-;CRMP2KI/KI) and GLAST knockout (GLAST-/-) mice with CRMP2KI/KI (GLAST-/-;CRMP2KI/KI) mice and compared them with GLAST+/- and GLAST-/- mice. pCRMP2 (S522) inhibition significantly reduced RGC loss and IRL thinning. These results suggest that the inhibition of CRMP2 phosphorylation could be a novel strategy for treating NTG.

Evolution of macular microvasculature and retinal layers alterations in patients with macula off retinal detachment after vitrectomy.

To examine the changes in retinal microvasculature in association with retinal layers' condition in patients with rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy (PPV). Participants in this study were 89 patients with macula off RRD, who were successfully treated with PPV and gas tamponade without internal limiting membrane peeling, in two centers. All participants underwent best corrected visual acuity (BCVA) measurement, slit-lamp examination, fundoscopy, spectral domain-optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) at week 5, month 3 and month 6 postoperatively. The fellow untreated eyes were also examined and served as control data. A statistically significant enlargement in foveal avascular zone (FAZ) in both superficial capillary plexus (SCP) and deep capillary plexus (DCP), accompanied with a statistically significant thinning of inner retinal layers, was noticed 5 weeks postoperatively. These changes, namely FAZ enlargement and thinning of inner retinal layers, in the operated eyes compared to the fellow eyes, remained unchanged till month 6 postoperatively. BCVA improved significantly from week 5 to months 3 and 6 postoperatively. The improvement in BCVA was associated with the gradual ellipsoid zone (EZ) recovery from the first (week 5) till the last examination (month 6). The FAZ enlargement in the operated eyes was accompanied with a statistically significant thinning in the inner retinal layers. Inter-correlation of BCVA and EZ integrity was noticed.

Staging and optical coherence tomography characteristics of gyrate atrophy of choroid and retina

This photo essay describes the optical coherence tomography (OCT) characteristics seen in gyrate atrophy (GA). A 39-year-old female presented with decreased night vision and peripheral vision, best-corrected visual acuity of 20/60 N10 and 20/40 N8 in both eyes, respectively. Fundus examination showed large confluent areas of chorioretinal atrophy involving the disc and leaving an annular zone of the normal retina at the macula. OCT of the macula of the right eye showed hyporeflective cystic spaces in the inner retina and epiretinal membrane, and the left eye was normal while that through the GA showed loss of reflectivity from the nerve fiber layer, extensive loss of inner segment/outer segment layer, thinning of inner retinal layers, retinal pigment epithelium, and Bruchs membrane (BM) and increased visibility of large choroidal-like vessels which appear to be in close proximity to the interpreted BM.

Retinal ganglion cell ablation in guinea pigs

Guinea pigs are a common model of human ocular conditions; however, their visual function has not been fully characterized. The purpose of this study was to determine the contributions of retinal ganglion cells to structural and functional measures in guinea pigs. Healthy adult guinea pigs (n = 12) underwent unilateral optic nerve crush. Retinal structure was assessed with spectral domain optical coherence tomography (OCT), and thickness of the ganglion cell/nerve fiber layer (GC/NFL) was determined. Visual function was assessed with optomotor tracking of a drifting grating and light adapted electroretinograms (ERGs). From flash ERGs, a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed. From pattern ERGs, N1P1 and P1N2 were analyzed. Histological studies were done at various time points for ganglion cell quantification. Optomotor tracking was absent in optic nerve crush eyes following optic nerve crush. Significant thinning of the GC/NFL was evident four weeks following the crush. Flash ERGs revealed a significant reduction in the OP1 amplitude two weeks following crush (P < 0.01) and in the PhNR amplitude six weeks following crush (P < 0.01). There were no significant changes in a-wave, b-wave, or pattern ERG responses (P > 0.05 for all). In vivo OCT imaging showed progressive thinning of inner retinal layers. Ganglion cell density, quantified histologically, was significantly reduced by 75% in the optic nerve crush eye compared to the control eye at four weeks following crush. These findings indicate that retinal ganglion cells contribute to the PhNR and OP1 components of the full field flash ERG, but not significantly to the pattern ERG in guinea pigs. This study demonstrates that OCT imaging and full field flash ERGs are valuable in assessing retinal ganglion cell loss in vivo in guinea pigs and will help to further establish the guinea pig as a model of human ocular pathologies.

Gene Therapy with Single-Subunit Yeast NADH-Ubiquinone Oxidoreductase (NDI1) Improves the Visual Function in Experimental Autoimmune Encephalomyelitis (EAE) Mice Model of Multiple Sclerosis (MS).

Mitochondrial dysfunction mediated loss of respiration, oxidative stress, and loss of cellular homeostasis contributes to the neuronal and axonal degenerations permanent loss of function in experimental autoimmune encephalomyelitis model (EAE) of multiple sclerosis (MS). To address the mitochondrial dysfunction mediated visual loss in EAE mice, self-complementary adeno-associated virus (scAAV) containing the NADH-dehydrogenase type-2 (NDI1) complex I gene was intravitreally injected into the mice after the onset of visual defects. Visual function assessed by pattern electroretinogram (PERGs) showed progressive loss of function in EAE mice were improved significantly in NDI1 gene therapy-treated mice. Serial optical coherence tomography (OCT) revealed that progressive thinning of inner retinal layers in EAE mice was prevented upon NDI1 expression. The 45% optic nerve axonal and 33% retinal ganglion cell (RGC) loss contributed to the permanent loss of visual function in EAE mice were ameliorated by NDI1-mediated prevention of mitochondrial cristae dissolution and improved mitochondrial homeostasis. In conclusion, targeting the dysfunctional complex I using NDI1 gene can be an approach to address axonal and neuronal loss responsible for permanent disability in MS that is unaltered by current disease modifying drugs.

Retinal pathology in experimental optic neuritis is characterized by retrograde degeneration and gliosis

The exact mechanisms and temporal sequence of neurodegeneration in multiple sclerosis are still unresolved. The visual pathway including its unmyelinated retinal axons, can serve as a prototypic model of neurodegeneration in experimental optic neuritis. We conducted a longitudinal study combining retinal imaging through optical coherence tomography (OCT) with immunohistochemical analyses of retinal and optic nerve tissue at various time points in experimental autoimmune encephalomyelitis (EAE).Inner retinal layer (IRL) thickness was measured in 30 EAE and 14 healthy control C57BL/6 J mice using OCT. Distribution of marker proteins was assessed by immunofluorescence staining and retinal mRNA levels were assayed using real-time PCR. Histological morphology was evaluated on light and electron microscopy images.Signs of inflammatory edema 11 days post immunisation coincided with IRL thickening, while neuro-axonal degeneration throughout the disease course contributed to IRL thinning observed after 20 days post immunisation. Retinal pathology, including axonal transport impairment, was observed early, prior to cellular infiltration (i.e. T-cells) in the optic nerve 11 days post immunisation. Yet, the effects of early retinal damage on OCT-derived readouts were outweighed by the initial inflammatory edema. Early microglial activation and astrocytosis was detected in the retina prior to retinal ganglion cell loss and persisted until 33 days post immunisation. Müller cell reactivity (i.e. aquaporin-4 and glutamine synthetase decrease) presented after 11 days post immunisation in the IRL. Severe neuro-axonal degeneration was observed in the optic nerve and retina until 33 days post immunisation.Initial signs of retinal pathology subsequent to early glial activity, suggests a need for prophylactic treatment of optic neuritis. Following early inflammation, Müller cells possibly respond to retinal pathology with compensatory mechanisms. Although the majority of the IRL damage observed is likely due to retrograde degeneration following optic neuritis, initial pathology, possibly due to gliosis, may contribute further to IRL thinning. These results add morphological substrate to our OCT findings. The extent and rapid onset of axonal and neuronal damage in this model appears relevant for testing interventions scaled to human optic neuritis.

Microvascular Complications of Posttransplant Diabetes Mellitus in Kidney Transplant Recipients: A Longitudinal Study.

To assesses microvascular complications in renal transplant recipients with posttransplant diabetes mellitus (PTDM). In this observational study, patients with ≥5 years of PTDM were included from a cohort of 895 kidney recipients transplanted from 2000 through 2011. Diabetic retinopathy was evaluated by fundus photographs and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and estimated glomerular filtration rate (eGFR). Distal polyneuropathy was assessed by Michigan Protocol and 10 g-monofilament feet examinations. The Ewing protocol identified cardiovascular autonomic neuropathy. Renal transplant recipients without PTDM diagnosis (NPTDM) were considered controls. After 144.5 months of follow-up, 135 (15%) patients developed PTDM, and 64 had a PTDM duration ≥5 years. None of the patients with PTDM presented diabetic retinopathy at fundus photographs, but thinning of inner retinal layers was observed with OCT. More than 60% of patients with PTDM had distal polyneuropathy (OR, 1.55; 95% CI, 1.26 to 1.91; P < 0.001). Cardiovascular reflex tests abnormalities were similar between patients with PTDM and NPTDM (P = 0.26). During the first year and 8.5 ± 3.0 years after renal transplantation, eGFR and PCR did not differ significantly between patients with PTDM or NPTDM. This longitudinal study assesses microvascular complications in renal transplant patients with PTDM. A lower than expected prevalence as well as a different clinical course of the complications was observed. PTDM seems to be a unique type of diabetes, and its consequences may be milder than expected in type 1 and type 2 diabetes.

Different Course of the Microvascular Complications of Diabetes Mellitus in Kidney Transplant Recipients with Posttransplant Diabetes—A Longitudinal Study

Objective: This study assessed microvascular complications (MC) occurrence in renal posttransplant diabetes mellitus (PTDM). Methods: Patients ≥ 5 years of PTDM were included from a cohort of 895 kidney recipients (KR) transplanted in 2000-2011. Diabetic retinopathy (DR) was evaluated by fundus photographs (FP) and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and eGFR. Distal polyneuropathy (DPN) was assessed by Michigan Protocol/monofilament foot exam. Ewing protocol identified cardiovascular autonomic neuropathy (CAN). Controls were KR transplanted in the same period but without PTDM (NPTDM). Results: After 578 weeks, 135 (15%) KR developed PTDM, 64 with PTDM ≥ 5 years. None of PTDM KR presented DR at FP but thinning of inner retinal layers was observed with OCT (Figure 1). More than 60% of PTDM KR had DPN (OR 1.55; CI 1.26-1.91; p&amp;lt;0.001). Frequency of CAN was similar between PTDM and NPTDM KR (p=0.26). During the 1st year and after 8.5±3.0 years of transplantation, eGFR and PCR did not differ between groups. Conclusions: This is the first longitudinal study to assess MC in PTDM KR. A lower than expected prevalence as well as a different clinical course of the MC was observed. PTDM seems to be a unique type of DM and its consequences may be milder than expected in type 1 and type 2 DM. Disclosure T.M. Londero Gai: None. L.S. Giaretta: None. R.C. Manfro: None. L.H. Canani: None. D. Lavinsky: None. C.B. Leitao: None. A. Bauer: None.

Neuroprotective effect of He-Ying-Qing-Re formula on retinal ganglion cell in diabetic retinopathy

Ethnopharmacology relevanceHe-Ying-Qing-Re Formula (HF) was empirically modified from Si-Miao-Yong-An Decoction (SD), which was recorded in the literature of Divine Doctor's Secret Transmission, and has been utilized for centuries to treat vasculopathy through clearing heat and accelerating bloodstream. HF has been used as an effective holistic treatment of diabetic retinopathy (DR) for decades and experimentally reported to ameliorate retinal condition in diabetic mice. Aim of the studyOur study aims to investigate the effect of HF in preventing sustained hyperglycemia and hyperlipidemia-associated retinal ganglion cell (RGC) cell death and its possible mechanism. Materials and methodsChromatographic fingerprint of HF was obtained upon the UPLC-based analytic system; Diabetic retinopathy was established in streptozotocin (STZ) injection-induced hyperglycemic mice; Alterations of retinal structure was assayed by H&E staining. Expression of PSD-95 and CHOP in retinae was assessed by immunofluorescence; RGC cell line (mRGC) was used for in vitro study. Cell death was analyzed by flow cytometry; Intracellular reactive oxygen species (ROS) was measured by 2′,7′-dichlorofluorescin diacetate (DCFDA); Apoptosis-related proteins and signaling were monitored with immunoblotting and colorimetric assay. ResultsChlorogenic acid, ferulic acid, and rutin were identified in HF. HF attenuates the loss of RGCs, thinning of inner retinal layers in diabetic mice. Furthermore, expressions of Brn3a and PSD-95 were restored while CHOP level was downregulated upon HF treatment. In vitro study, HF alleviates H2O2-induced apoptosis of mRGCs and loss of postsynaptic protein via scavenging ROS and suppressing ATF4/CHOP-mediated endoplasmic reticulum stress and mitochondria-related pro-apoptotic factors, probably as cleaved-caspase-3, and phospho-p38 mitogen-activated protein kinase (MARK). Meanwhile, both pro-survival protein levels like Bcl-2/Bcl-xL and postsynaptic protein of PSD-95 were upregulated upon HF treatment. ConclusionHF administration was a valid therapeutic approach for DR treatment, oriented at the blockade of endoplasmic reticulum- and mitochondria-dependent oxidative stress-induced retinal neurodegeneration including RGC apoptosis.

Thinning of Inner Retinal Layers after Vitrectomy with Silicone Oil versus Gas Endotamponade in Eyes with Macula-Off Retinal Detachment

Purpose: To evaluate retinal layer thickness with optical coherence tomography (OCT) in eyes with macula-off retinal detachment after silicone oil (SiO) or gas endotamponade. Procedures: Cross-sectional study of 40 eyes with macula-off rhegmatogenous retinal detachment that underwent vitrectomy. 20 eyes received SiO tamponade and 20 matched eyes received gas. 33 healthy fellow eyes served as controls. Macular spectral domain OCT was performed with automated layer detection in the 5 inner subfields of the Early Treatment Diabetic Retinopathy Study (ETDRS) map. Results: Comparing the SiO group with the gas group, the ganglion cell layer showed a significant thinning in all fields of the inner ring of the ETDRS map, the inner plexiform layer in the nasal, superior and temporal quadrants, and the outer plexiform layer in the nasal quadrant. Conclusions: Inner retinal layers in the fovea/parafovea were significantly thinner in the SiO group. Prospective studies are warranted to further elucidate possible retinal adverse effects of SiO tamponade.

DBA/2J mouse model for experimental glaucoma: pitfalls and problems.

The DBA/2J mouse has been described as a model for congenital experimental glaucoma. It develops anterior segment anomalies with synechiae and pigment dispersion leading to raised intraocular pressure and glaucomatous damage. However, there are serious practical considerations when using this model in longitudinal studies. We followed 118 mice from 12-48 weeks of age in a pharmaceutical trial. Here we report on the findings in control animals (n = 37). Intraocular pressure was measured weekly, electrophysiology and optical coherence tomography every 6 weeks. A subset also had invasive intraocular pressure measurements performed prior to euthanasia. Although intraocular pressure eventually rose by 9 months in most animals, tonometry was complicated by corneal calcification in the majority of animals rendering intraocular pressure measurement unreliable. Invasive intraocular pressure did not correlate with non-invasive measures. Loss of scotopic threshold response and thinning of inner retinal layers on optical coherence tomography was observed over time, suggesting glaucomatous damage, but this occurred in some animals without raised intraocular pressure. Poor pupil dilation significantly affected electrophysiology, optical coherence tomography and fundus imaging; 22% of animals developed major systemic complications leading to high dropout rate. The DBA/2J experimental glaucoma model shows variability in expression, and its pathological changes cause major difficulties in assessing disease progression. From our experience, the model presents significant challenges for drug studies in glaucoma, as there are many confounding factors: difficulty with accurate intraocular pressure measurement, in vivo imaging, and electrophysiology recording and a high dropout rate. In addition, there may be an underlying neurodegenerative process independent of intraocular pressure.

Vision loss under silicone oil tamponade.

We aimed to investigate frequency, time course and pathophysiology of vision loss in eyes with macula-on rhegmatogenous retinal detachment operated with vitrectomy and silicone oil tamponade. Fifteen eyes of 15 patients who had been operated with 5,000 centistoke silicone oil between 2006 and 2014 were included in a retrospective case series. Examinations included logMAR best corrected visual acuity (BCVA), visual field testing (VF), spectral domain optical coherence tomography (OCT), electrophysiology, and fluorescein angiography. Vision loss was seen in eight (53%) eyes of 15 patients with symptomatic central scotoma, which was confirmed by VF (5/6). Preoperative median BCVA of these patients was 0.15 (0.5 to 0), prior to oil removal 0.7 (1.0 to 0.5), and 6weeks post oil removal 1.0 (1.5 to 0.2). BCVA recovered in five patients to a median of 0.15 (0.5 to 0.1), and it remained 1.0 in three (20%) out of 15 eyes. OCT revealed significant thinning of the foveal and parafoveal combined nerve fiber, ganglion cell and inner plexiform layers in affected eyes (mean 58.3μm +/-13, horizontal scan through fovea, 500μm radius) compared to their healthy fellow eyes (mean 84.5μm +/-12.3; p < 0.01, n = 6 patients, 12 eyes) and compared to eyes with no vision loss under silicone oil. We find persisting vision loss in three out of 15 patients treated for macula-on rhegmatogenous retinal detachment with silicone oil tamponade. Thinning of inner retinal layers possibly evoked by silicone oil tamponade might be a pathophysiological explanation for vision loss in these patients.

En face swept-source optical coherence tomography detecting thinning of inner retinal layers as an indicator of capillary nonperfusion.

To report en face swept-source optical coherence tomography (SS-OCT) as a noninvasive detection modality for regions of retinal layer thinning that are potential indicators of retinal nonperfusion areas (NPAs) in patients with branch retinal vein occlusion (BRVO). Thirty-one eyes of 46 patients with BRVO showing a definite retinal NPA larger than 1 disc in diameter within the vascular arcades were included in this study. We calculated the overlapping correspondence ratio between presumed NPA, which appeared as a dark area in en face SS-OCT, and definite NPA in corresponding fluorescein angiography (FA) images. The correlation between brightness in en face SS-OCT images and corresponding ganglion cell complex (GCC) thickness determined by SD-OCT GCC maps was evaluated as well. Measured NPA size in FA and presumed NPA size in en face SS-OCT showed strong correlation (r = 0.746, p&lt;0.001) and colocalization. Reliable agreement between the 2 methods was confirmed by size comparisons (p = 0.11), with an overlapping correspondence ratio of 0.73. The results suggest that en face SS-OCT is a noninvasive and relatively reliable method for delineating retinal thinning as an indicator of NPAs in eyes with BRVO. Because SS-OCT can be performed without mydriasis, this procedure may be an option for evaluating NPAs on a screening basis and during follow-up to reduce the number of FA examinations that carry very rare, but potentially fatal, allergic side effects.

Inner and outer central retinal findings after surgery for rhegmatogenous retinal detachment using different spectral-domain optical coherence tomography devices

The aim of the study was to analyse macular changes after rhegmatogenous retinal detachment (RRD) repair using spectral-domain optical coherence tomography (SD-OCT). Forty eyes with macula-on and 27 eyes with macula-off RRD underwent scleral buckling or vitrectomy and were postoperatively imaged using 2 SD-OCT devices (Cirrus® HD-OCT, RTVue-100®). Measurement of total and inner macular thickness consisting of ganglion cell layer + inner plexiform layer (GCL-IPL) using Cirrus or retinal nerve fibre layer + ganglion cell layer + inner plexiform layer (RNFL-GCL-IPL) using RTVue was performed. Results of inner macular thickness were compared with image results of 40 healthy controls. Qualitative analysis of inner and outer retinal layers was additionally assessed. Measurement of overall retinal thickness within the 9 ETDRS sectors was highly correlated between both OCTs (Pearson's r, range 0.88-0.99; p < 0.001). Correlation of RNFL-GCL-IPL complex between OCTs was excellent in both surgery groups (Pearson's r, range 0.73-0.88; p < 0.001) and normal controls (Pearson's r, range 0.79-0.90; p < 0.001). The RNFL-GCL-IPL complex was thicker in both surgery groups compared to normal controls using Cirrus. Outer retinal findings of macula-off patients were seen in four eyes (14.8 %). Visual acuity (VA) significantly improved in both groups independent of preoperative VA or duration of symptoms. Agreement between both OCTs was excellent for overall and inner retinal thickness, although RTVue measured a thicker RNFL-GCL-IPL complex. Thinning of inner retinal layers as a potential cause of poor VA was rarely detected, possibly due to tractional changes at the vitreomacular interface. VA improved even in patients with macula-involving RRD.

Correlation of Inner Retinal Thickness Evaluated by Spectral-Domain Optical Coherence Tomography and Contrast Sensitivity in Parkinson disease

To compare inner retinal layer (IRL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) and contrast sensitivity (CS) in patients with Parkinson disease (PD) and in healthy control (HC) subjects. Consecutive patients with and without PD were prospectively analyzed using SD-OCT and Pelli-Robson CS testing. SD-OCT IRL (ganglion-cell complex) thickness, consisting of the nerve fiber layer, ganglion cell layer, and inner plexiform layer, was segmented using an RTVue Model-RT100 with an EMM5 scan parameter covering a 5.0 × 5.0 mm cube centered on the fovea. Thickness voxel measurements at 0.25-mm intervals at sequential radial distances from the foveola were acquired horizontally and vertically. SD-OCT thickness raw data files were imported and analyzed within MATLAB (version 7.10.0). A database of CS scores and IRL thickness values by foveal location was constructed and statistically evaluated using JMP 10 (SAS Institute, Inc, Cary, NC). The results were compared between 28 eyes of 14 patients with PD and 28 eyes of 14 HC subjects. Controlling for age, mean CS scores of monocular right and randomized eyes were statistically lower in PD eyes (P < 0.05). IRL was significantly thinner in PD eyes than in HC eyes at several distances from the foveola (P < 0.05). The most numerous and significant thickness differences by diagnosis were located in the superior quadrant at a distance of 1.00-1.75 mm from the foveal center (17 μm; P < 0.01, maximum significant thickness difference and P value). Correlation was demonstrated between monocular CS and IRL thickness by diagnosis at multiple foveal locations for HC eyes as follows: nasal quadrant, 0.75-1.00 mm (P < 0.02); temporal quadrant, 0.50-1.00 mm (P < 0.05); superior quadrant, 1.00 mm (P < 0.05); and inferior quadrant, 1.00 mm (P < 0.03). No significant correlation was found between monocular CS and IRL thickness within PD subjects (P > 0.05 for each foveal location measured). CS and foveal IRL thickness are decreased in patients with PD. CS and IRL thickness correlated in HC subjects; however, no such correlation was demonstrated in PD. The functional deficit of dopaminergic interneurons, including amacrine cells, may outstrip the anatomic structural changes in the inner retina of PD patients. Inner retinal atrophic changes may underlie the pathogenesis of CS deficit and IRL thinning in PD.

Spectral domain optical coherence tomography for early detection of retinal alterations in patients using hydroxychloroquine

Objective:To determine whether early toxic effects from hydroxychloroquine (HCQ) could be detected by spectral-domain optical coherence tomography (SD-OCT) before symtomatic visual loss occured.Materials and Methods:Fifteen subjects with a history of the chronic use of hydroxychloroquine monotherapy for less than five years without fundus changes (group 1) and 15 visually normal healthy subjects (group 2) were enrolled in this study. All participants underwent systemic and ocular examination, visual field testing, and macular scan imaging using SD-OCT.Results:There were no significant differences in sex and ages between the groups (P > 0.05). Mean duration of HCQ usage in group 1 was 2.5 ± 1.34 (range:1-5) years. Visual field testing with central 10-2 threshold program was normal in all subjects. Inner retinal thickness in parafoveal and perifoveal area were found to be significantly lower in group 1 compared to group 2 (P < 0.01 for perifoveal, P < 0.05 for parafoveal retinal measurements). However, significant thinning was demonstrated only in full retinal thickness of perifoveal area in group 1 compared to group 2 (P: 0.013). Parafoveal and perifoveal inner retinal thickness measurements of inferior quadrants were significantly reduced in group 1 compared to group 2 (P < 0.01).Conclusion:Significant thinning of inner retinal layer especially in parafoveal and perifoveal areas in the absence of clinical fundus changes was observed in our study. We consider that SD-OCT may determine when inner retinal thinning starts in these patients and may contribute a quantitative approach to the early diagnosis and progression of retinal changes.

Neuroprotective effect of resveratrol prophylaxis on experimental retinal ischemic injury

The purpose of the present study was to investigate whether systemically administered resveratrol can protect against acute retinal ischemic reperfusion injury. Two groups of adult male Sprague Dawley rats (n = 6 per group) were used for this study. Resveratrol (30 mg/kg) or an equal volume of vehicle (30% Solutol HS 15 in 0.9% saline) was administered daily for 5 days via intraperitoneal injection. On the third day of treatment, retinal ischemic injury was induced by elevation of intraocular pressure for 45 min. Prior to resveratrol administration and one-week following ischemic insult, retinal function was measured by scotopic electroretinography (ERG). Retinas were harvested and morphologically analyzed one week after ischemic insult. ERG a- and b-wave amplitudes were significantly reduced following ischemic reperfusion injury. Resveratrol treatment attenuated ischemic-induced loss of retinal function. In control vehicle-treated rats, ischemic reperfusion injury elicited marked thinning of inner retinal layers. Resveratrol prophylactic treatment reduced ischemia-mediated thinning of the whole retina and in particular the inner retinal layers. Therefore, resveratrol may have therapeutic value for the management of retinal ischemic disorders.

Visual loss after use of intraocular silicone oil associated with thinning of inner retinal layers

To investigate the incidence and cause of severe visual loss following use and removal of intraocular silicone oil (SiO) after uncomplicated vitrectomy and SiO injection for primary rhegmatogenous retinal detachment (RRD). Consecutive case series of 216 patients operated with vitrectomy for primary RRD in 2004-2005. In 162 eyes, SiO (5500 centiStoke) had been used as intravitreal tamponade and in 54 eyes gas (perflouropropane, C(3) F(8) ) had been used. Following chart review, we identified 16 eyes in 16 patients (nine SiO eyes, seven gas eyes) with macula-on and documented visual acuity ≥6/12 before surgery, where SiO had been removed, cataract surgery performed and no re-detachment had occurred. Examinations included best-corrected visual acuity (BCVA) and high-definition optical coherence tomography (OCT) of the macular area. Preoperative characteristics were identical between SiO and gas eyes. Postoperative BCVA was significantly worse in SiO eyes (>6/24) compared to gas eyes (>6/7.5), p = 0.005. Three of 9 (33%) SiO eyes had final BCVA ≤6/60 and 67% had final BCVA ≤6/12. No gas eyes had final BCVA <6/9. Macular OCT revealed thinning of inner retinal layers in SiO-operated eyes (5148 pixels) compared to gas-operated eyes (6897 pixels), p < 0.002. No other visually significant structural differences were found. Severe visual loss after SiO use was observed in 1/3 of patients with otherwise good visual potential. The visual loss was associated with a significant reduction in inner retinal thickness indicating neuronal cell loss in the macular area as a possible explanation.

Granulocyte colony-stimulating factor facilitates recovery of retinal function following retinal ischemic injury

The purpose of the present study was to investigate whether systemically administered granulocyte colony-stimulating factor (G-CSF) can protect against acute ischemic reperfusion injury. Two groups of anesthetized adult male Lewis rats ( n = 8 per group) were subjected to an acute (45 min) episode of retinal ischemic injury followed by subcutaneous administration of vehicle (5% dextrose) or G-CSF (0.1 mg/kg/day) once per day × 5 days. Prior to and one week following ischemic insult, retinal function was measured by scotopic electroretinography (ERG). Retinas were harvested and morphologically analyzed one week after ischemic insult. ERG a- and b-wave amplitudes were significantly reduced following ischemic reperfusion injury. G-CSF treatment attenuated ischemic-induced loss of retinal function. In control vehicle-treated rats, ischemic reperfusion injury elicited marked and selective thinning of inner retinal layers while only minimally affecting outer retinal layers. Therapeutically administered G-CSF minimized ischemic-mediated thinning of whole retina and inner retinal layers. G-CSF may be of therapeutic interest for the management of retinal ischemic disorders.