Alterations Of Retinal Layers Research Articles

Protective efficacy of nafronyl in diabetic retinopathy through targeted inhibition of key enzymes.

Diabetic retinopathy is governed by abnormal apoptosis, increased capillary pressure, and other linked pathology that needs an efficient treatment by multitargeted approaches. Thus, the current study aimed to explore the potential of inhibition of targeted enzymes (DPP4, ACE-2, and aldose reductase) and free radical scavenging capabilities of selected compounds (nafronyl or naftidrofuryl) through in silico and in vivo investigations. Significant binding energies were observed in complexes of aldolase reductase, angiotensin type 1 receptor, and DPP4 against the nafronyl and sitagliptin more than -7.5kcal/mol. Further validation of free energy was confirmed by calculations of molecular mechanics Poisson-Boltzmann surface area (MMPBSA), and configurational stabilities examined by PCA (principal component analysis). Additionally, drug-likeness was examined by the Swiss ADME web tool, which showed significant findings. Consequently, in vivo experimentations showed significant inflammation and alterations in retinal layers of inner plexiform (inner limiting membrane, nerve fibers, and ganglionic cells), inner nuclear layer (bipolar cells and horizontal cells), and photoreceptors cells. Whereas the treatments (nafronyl and sitagliptin) caused significant improvements in the histoarchitecture of the retina. Additionally, the HOMA indices (IR-insulin resistance, sensitivity, and β cells functioning) and levels of free radicals were significantly altered in the diabetic control group in comparison to intact control. Nafronyl administration showed significant ameliorations in HOMA indices as well as antioxidant levels. Based on the results, it can be concluded that nafronyl efficiently interacts with target enzymes, which may result in potent inhibition and ameliorations in retinal histology as well as glucose homeostasis and antioxidants.

Evaluation of Structural Retinal Layer Alterations in Retinitis Pigmentosa.

Objective: This study aimed to analyze retinal layers in the macular region using spectral-domain optical coherence tomography (SD-OCT). Additionally, we examined the retinal vascular plexus densities of the eyes using optical coherence tomography angiography (OCT-A), specifically in patients with retinitis pigmentosa (RP). Methods: In the study, 36 eyes from patients with retinitis pigmentosa (RP) and 36 eyes from healthy controls were included. Measurements involved assessing the thicknesses of each retinal layer at the central fovea, parafoveal, and perifovea using spectral domain optical coherence tomography (SD-OCT). Moreover, the study involved the evaluation of retinal capillary plexus densities (RCPD), encompassing deep capillary plexus density values, superficial capillary plexus, and radial peripapillary capillary plexus. This assessment was performed using optical coherence tomography angiography (OCT-A). Results: No statistically significant difference in retinal thickness was found in the central fovea between the two groups. The thicknesses of the INL, OPL, and PRL in the parafoveal regions as well as the RPE in the perifoveal regions increased in the RP group. Nonetheless, the ONL, IPL, GCL, and RNFL demonstrated reduced thickness in both the perifoveal and parafoveal areas. The OCT-A findings indicated that patients with RP exhibited lower values for all RCPD. Conclusion: The retinal layers and RCPD were significantly impacted at varying rates of RP. It is essential to acknowledge that this alteration may be significant in the context of the retinal findings in patients with RP. Abbreviations: SD-OCT = Spectral-domain optical coherence tomography, OCT-A = Optical coherence tomography angiography, RP = Retinitis pigmentosa, ETDRS = Early Treatment Diabetic Retinopathy Study, SD = standard deviation, TRT = Total Retinal Thickness, IRT = Inner Retinal Thickness, ORT = Outer Retinal Thickness, RNFL = Retinal Nerve Fiber Layer, GCL = Ganglion Cell Layer, IPL = Inner Plexiform Layer, INL = inner nuclear layer, OPL = Outer Plexiform Layer, ONL = Outer Nuclear Layer, PRL = Photoreceptor layer, RPE = Retinal Pigment Epithelium, µm = micrometer, PaFoSu = parafovea superior, PeFoSu = perifovea superior, PaFoNa = parafovea nasal, PeFoNa = perifovea nasal, PaFoTe = parafovea temporal, PeFoTe = perifovea temporal, PaFoIn = parafovea inferior, PeFoIn = perifovea inferior.

Traumatic macular hole repair through topical dorzolamide

Traumatic macular holes (MHs) still have a guarded prognosis. Whether spontaneous closure or early surgical intervention leads to a more favorable outcome is unclear. Topical therapy with carbonic anhydrase inhibitors was reported to be a non-invasive but effective treatment for traumatic MHs. A 17-year-old boy, whose face was injured by a firework explosion, presented to our emergency department with decreased vision in his left eye (20/125). A bio-microscopic examination revealed a vitreous hemorrhage that partially obscured the fundus. Optical coherence tomography (OCT) revealed an MH in the fovea with mild intra-retinal edema and juxtafoveal outer retinal layer alterations. Dorzolamide (2%) was administered four times per day. Two weeks later, OCT revealed a closed MH, and the patient's visual acuity had improved to 20/30 at 2 months following the incident. Topical aqueous suppression therapy may potentiate the closure of traumatic MHs by reducing the amount of intra-retinal fluid. It can serve as a non-invasive therapy for small traumatic MHs, especially those with the intra-retinal fluid, or as a temporary therapy before a scheduled operation.

Subclinical alterations in retinal layers and microvascular structures with OCTA in ANCA-associated vasculitides

ABSTRACT Purpose Using OCTA, investigate the capillary network and retinal layers in granulomatosis with ANCA associated vasculitis (AAV) patients who did not manifest apparent ocular involvement and compare the findings with healthy subjects. Method The present study, which is designed as a prospective and case-control study, includes 22 AAV patients and 35 control participants. OCTA parameters were noted. Results In most of the regions, AMT, RNFL and GC-IPL thicknesses were significantly lower in the AAV group than in the control group. While the vascular indices were lower in the AAV group, except for the center 1 mm region, the FAZ parameters were similar between the two groups. Conclusion In AAV patients, subclinical changes in the retinal layers and superficial vascular plexus have been shown. In the future maybe a non-invasive method such as OCTA will become available in scoring systems for prognosis determination in AAV.

Evaluation of subclinical alterations in retinal layers and microvascular structures with OCT and OCTA in healthy young short-term smokers

PurposeTo detect the changes that can be determined with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in young and short-term smokers. MethodIn this cross-sectional, observational, and comparative study, 45 "healthy" smokers and 45 healthy non-smoker control participants were included. Those with a smoking history between 1 year to 5 years and an average of 10–30 cigarettes per day were included in the study. OCT and OCTA measurements were made at least 60 min after smoking and at least 8 h after caffeine-containing beverages in order to end the effect of nicotine on systemic and retinal blood flow in the smoking group. ResultsThe mean smoking period was 2.2 ± 0.13 years. Mean macular thickness(MMT), retinal nerve fiber layer(RNFL), and choroidal thickness(Cht) were significantly lower in the smoker group, while ganglion cell-inner plexiform layer(GC-IPL) thickness was higher. Vessel density(VD) values were similar between groups, while perfusion density(PD) values were significantly higher in the smoker group. There were significant correlations between MMT and outer VD, outer PD, foveal avascular zone(FAZ) perimeter and circularity index. FAZ area and central VD and PD were inversely correlated. Also, FAZ circularity index and subfoveal, nasal, and temporal ChTs were positively correlated. ConclusionDespite the short-term smoking, ischemic effects were observed in retinochoroidal and vascular structures.

Histological Effects of Intravitreal Injection of Antifungal Agents in New Zealand White Rabbits: An Electron Microscopic and Immunohistochemical Study.

Fungal endophthalmitis is a serious and vision-threatening infection which requires an immediate and effective treatment approach. Our research aims to elucidate the histological effects of the intravitreal injection of the maximum safe dosage of voriconazole and micafungin on retina. Six albino New Zealand White Rabbits were used. In experimental animals, a solution of voriconazole (Group V) or micafungin (Group M) was intravitreally injected in the right eye, while in control animals, balanced salt solution was intravitreally injected in the left eye (Group C). Euthanasia was performed ten days post injection and the retina was removed and prepared for histological examination with a light and electron microscope. Eosin-hematoxylin staining did not reveal any pathological changes in any of the samples examined. The immunohistochemical staining for Tumor Necrosis Factor alpha (TNF-a) marker was detected as negative in all samples, while Interleukin 6 (IL-6) marker was detected as mild only in the group injected with voriconazole. Electron microscopy revealed several ultrastructural alterations in retinal layers in both groups of experimental animals. Histological retinal lesions, revealed with electron microscopy in the present investigation, raises the question of the safe usage of these antifungal agents in the treatment of fungal intraocular infections in the future.

Alteration of retinal layers in healthy subjects over 60 years of age until nonagenarians.

PurposeTo assess alterations of retinal layers in healthy subjects over 60 years old.MethodsRetinal layers of 160 healthy subjects (aged 60–100 years) without any retinal pathology were imaged using spectral domain optical coherence tomography. Mean thickness of retinal nerve fiber layer, ganglion cell/inner plexiform layer (GCLIPL), inner nuclear layer, outer plexiform layer/outer nuclear layer, photoreceptor complex (PR) and retinal thickness (RT) were measured in a 3.45 mm grid. Correlations between age and layers were estimated and linear regression equations were calculated. Different age-groups (60–69, 70–79, 80–89 years and nonagenarians, each group with 40 participants) were compared.ResultsSignificant age-thickness correlations were observed for GCLIPL (P<0.001, r=−0.394), PR (P<0.001, r=−0.370) and RT (P<0.001, r=−0.290). A comparison between age groups 60–69 years and nonagenarians showed no significant thickness alteration of retinal nerve fiber layer (21.80±2.18 μm vs 22.82±2.97 μm, P=0.163), inner nuclear layer (37.23±3.02 μm vs 36.01±3.24 μm, P=0.07) and outer plexiform layer/outer nuclear layer (104.95±6.56 μm vs 104.23±7.59 μm, P=0.567), while GCLIPL (83.35±7.35 μm vs 74.38±9.09 μm), PR (83.03±3.31 μm vs 79.34±2.09 μm) and RT (330.64±12.63 μm vs 316.83±18.35 μm) showed a significant decrease (P<0.001 for all).ConclusionOur study provides normative data of alterations of retinal layers for persons aged 60 years to nonagenarians and indicates a continuous decrease of RT, PR, and GCLIPL. This data may be useful for clinical trials investigating macular diseases in older patients.

Acute and Protracted Cell Death in Light-Induced Retinal Degeneration in the Canine Model of Rhodopsin Autosomal Dominant Retinitis Pigmentosa.

PurposeTo characterize a light damage paradigm and establish structural and immunocytochemical measures of acute and protracted light-induced retinal degeneration in the rhodopsin (RHO) T4R dog model of RHO–autosomal dominant retinitis pigmentosa (ADRP).MethodsRetinal light damage was induced in mutant dogs with a 1-minute exposure to various light intensities (0.1–1.0 mW/cm2) delivered with a Ganzfeld stimulator, or by fundus photography. Photoreceptor cell death was assessed by TUNEL assay, and alterations in retinal layers were examined by histology and immunohistochemistry 24 hours and 2 weeks after light exposure. Detailed topographic maps were made to document changes in the outer retinal layers of all four retinal quadrants 2 weeks post exposure.ResultsTwenty-four hours post light exposure, the severity of photoreceptor cell death was dose dependent. Immunohistochemical analysis revealed disruption of rod outer segments, focal loss of the RPE integrity, and an increase in expression of endothelin receptor B in Müller cells with the two highest doses of light and fundus photography. Two weeks after light exposure, persistence of photoreceptor death, thinning of the outer nuclear layer, and induction of Müller cell gliosis occurred with the highest doses of light.ConclusionsWe have characterized outcome measures of acute and continuing retinal degeneration in the RHO T4R dog following light exposure. These will be used to assess the molecular mechanisms of light-induced damage and rescue strategies in this large animal model of RHO-ADRP.

Retinotoxicity of Hydroxychloroquine: Is It Possible to Demonstrate by Spectral Domain Optical Coherence Tomography Before Development? A Cross Sectional Investigation

Objectives: This study aims to evaluate the alterations of retinal layers in rheumatic patients treated with hydroxychloroquine but without the signs or symptoms of retinopathy by using spectral domain ocular coherence tomography (SD-OCT). Patients and methods: The retinal layers of a total of 402 eyes including 114 patients treated with hydroxychloroquine (for rheumatoid arthritis (n=40), Sjogren’s syndrome (n=47) and connective tissue diseases (n=27) and age-matched 87 healthy controls were evaluated with SD-OCT. The macular cube protocol, optic disc cube protocol and horizontal and vertical HD 5-line raster scan protocol were applied. The measured parameters were compared between hydroxychloroquine users and healthy control group. The results of these parameters were also compared with other disease groups using hydroxychloroquine. The correlation of these parameters with the duration of drug consumption and dose was assessed. Results: All layers of outer fovea, superior and inferior quadrants of retinal nerve fiber layers of hydroxychloroquine users were thinner than nonusers. Connective tissue disease group had longer duration and higher cumulative dose of hydroxychloroquine than other diagnostic groups. This group had thinner mean retinal nerve fiber layers values than the other groups as well. There were significant and negative correlations between cumulative dose of drug and parafoveal region thickness of outer fovea and inferior quadrant of retinal nerve fiber layers. Thickness of parafoveal and perifoveal layers was negatively correlated with the dose of drug per kg of body weight. Conclusion: Our study results show that SD-OCT may be the golden standard technique for the follow-up of antimalarial-induced retinotoxicity in

A systematic correlation of morphology and function using spectral domain optical coherence tomography and microperimetry in patients with geographic atrophy

AimsThis study has been designed to describe the functional impact of distinct pathologies within the retinal layers in patients with geographic atrophy (GA) by means of a point-to-point correlation between...

FRI0504 Retinotoxicity of hydroxychloroquine; is it possible to demonstrate by spectral domain optical coherence tomography before development? a cross sectional investigation

BackgroundHydroxychloroquine is an antimalarial drug, which has been used for the treatment of autoimmune disorders as rheumatoid arthritis, connective tissue disease and Sjögren’s syndrome. Potential retinotoxicity of the antimalarial drugs...

Near-infrared and Short-wavelength Autofluorescence in Resolved Central Serous Chorioretinopathy: Association With Outer Retinal Layer Abnormalities

To evaluate the correlation between changes in fundus autofluorescence (AF) measured using 2 different sources (near-infrared fundus autofluorescence from melanin and short-wavelength fundus autofluorescence from lipofuscin) with changes in spectral-domain optical coherence tomography (SD OCT) and fluorescein angiography in resolved central serous chorioretinopathy (CSC). Retrospective, observational case study. A total of 91 eyes from 86 patients with a history of resolved CSC and abnormal AF imaging findings were included. In addition to AF, patients were assessed by means of SD OCT and fluorescein angiography. Outer retinal layer alterations in OCT images and abnormalities in fluorescein angiography were analyzed and correlated with the corresponding AF data. All eyes with abnormal near-infrared AF showed a hyperfluorescent angiography window defect in the corresponding area. There was a significant association between the OCT and short-wavelength AF findings. An abnormal short-wavelength AF signal was significantly associated with loss of the ellipsoid portion of the inner segments (EPIS, previously known as the junction between the inner and outer segments of the photoreceptors) on SD OCT (χ(2) test; P < .0001). Near-infrared AF could not predict the status of EPIS without the short-wavelength AF image. Outer retinal layer changes in OCT images can be predicted by analyzing both short-wavelength AF and near-infrared AF images. Abnormal changes in the short-wavelength AF image were predictive of EPIS damage.

Investigation of the retinal biocompatibility of acid violet for chromovitrectomy

The primary objective was to investigate the retinal biocompatibility of acid violet (AV) as a vital dye for chromovitrectomy. The secondary objective was to evaluate the capacity of AV to stain the anterior capsule of the lens. An amount of 0.05 ml of 0.25 g/l and 0.5 g/l AV was injected intravitreally in the OD, while balanced salt solution (BSS) was applied in the OS for control. Clinical examination and histology with light microscopy (LM) were performed after 7 days. Retinal cell layers were evaluated for morphologic alterations and number of cells. The electroretinographic (ERG) changes were assessed at baseline and 7 days. In another part of the study, 0.1 ml of 0.25 g/l AV was injected into the anterior chamber of ex-vivo porcine eyes, and its capacity to stain the anterior capsule was determined. Cadaveric eyes were used to test the capacity of AV to stain the internal limitant membrane (ILM) during vitrectomy. The gross histopathologic appearance of the retina, choroids, sclera, and optic nerve was within normal limits, without any signs of severe retinal necrosis or cystic degeneration. AV caused no substantial retinal alterations in retinal layers by LM at either the lower or higher dose when compared with the control eye. The injection of AV did not induce considerable ERG alterations. The violet dye stained the anterior capsule after anterior chamber injection and the ILM, allowing a safer capsulorrhexis and vitrectomy. Acid violet may be safe for the retina at concentrations of 0.25 and 0.50 g/l after intravitreous injection, and may be used as a vital dye for staining the anterior capsule and the ILM.

Erythropoietin Protects the Developing Retina in an Ovine Model of Endotoxin-Induced Retinal Injury

Intrauterine infection is a common antecedent of preterm birth. Infants born very preterm are at increased risk for neurologic dysfunction, including visual deficits. With increasing survival of very preterm infants, there is a need for therapies that prevent adverse neurologic outcomes. Using an ovine model, the authors investigated the neuroprotective potential of recombinant human erythropoietin (rhEPO) on retinal injury induced by intrauterine inflammation. At 107 ± 1 days of gestational age (DGA), chronically catheterized fetal sheep received either of the following on 3 consecutive days: intravenous (IV) bolus dose of lipopolysaccharide (LPS; ∼0.9 μg/kg; n = 8); IV bolus dose of LPS, followed at 1 hour by 5000 IU/kg rhEPO (LPS + rhEPO; n = 8); rhEPO alone (n = 5). Untreated fetuses (n = 8) were used for comparison with the three treatment groups. Fetal physiological parameters were monitored. At 116 ± 1 DGA, fetal retinas were assessed quantitatively for morphologic and neurochemical alterations. Exposure to LPS alone, but not to rhEPO alone, resulted in fetal hypoxemia and hypotension (P < 0.05). Exposure to LPS alone caused retinal changes, including reductions in thickness of the inner nuclear layer (INL), somal areas of INL neurons, process growth in the plexiform layers, and numbers of ganglion and tyrosine hydroxylase immunoreactive (TH-IR) dopaminergic amacrine cells. Treatment of LPS-exposed fetuses with rhEPO did not alter the physiological effects of LPS but significantly reduced alterations in retinal layers and ganglion and TH-IR cell numbers. rhEPO treatment was beneficial in protecting the developing retina after LPS-induced inflammation. Retinal protection could occur by the antiapoptotic or anti-inflammatory actions of EPO.

Outer Retinal Hyperreflective Spots on Spectral-Domain Optical Coherence Tomography in Macular Telangiectasia Type 2

To analyze focal hyperreflective morphologic alterations in outer retinal layers in patients with type 2 idiopathic macular telangiectasia (MacTel type 2) using spectral-domain optical coherence tomography (SD OCT). Cross-sectional case-control study. Forty-one patients with MacTel type 2. Anatomic layers were evaluated and compared with those of controls of similar age. Simultaneous SD OCT scans were obtained with a combined confocal scanning laser ophthalmoscope for simultaneous tomographic and topographic in vivo imaging (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). Morphologic alterations in the retinal layers secondary to MacTel type 2. Hyperreflective spots in the outer retina of MacTel type 2 patients were detected in all stages of disease using the SD OCT. Their presence was confined to the foveolar and parafoveolar region. The phenomenon also was detected in a monozygotic twin in an eye with no typical angiographic sign of the disease. A hyperreflective haze was detected in the vicinity of a disruption of the hyperreflective OCT line that is assumed to represent the line between the photoreceptor inner and outer segments and interdigitation of the outer segments and the retinal pigment epithelium. No corresponding pathologic features could be identified by biomicroscopy, time-domain OCT, or confocal scanning laser ophthalmoscope imaging. Crystalline deposits and intraretinal migration of pigmented cells were distinguishable because of differences in shape, reflectivity, and location. Hyperreflective spots were identified in outer retinal layers of patients with MacTel type 2 in all disease stages. It is suggested that this phenomenon represents an early sign of a neurodegenerative process. Secondary assumptions include extravasated deposits or vascular abnormalities. The pathologic features are indicative of an active disease process before the disease manifests by typical fluorescein angiographic signs. Proprietary or commercial disclosure may be found after the references.

Correlation between Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence at the Margins of Geographic Atrophy

To study the appearance of margins of geographic atrophy in high-resolution optical coherence tomography (OCT) images and to correlate those changes with fundus autofluorescence (FAF) imaging. Retrospective, observational case study. Patients with geographic atrophy secondary to dry age-related macular degeneration were assessed by means of spectral-domain OCT (Spectralis Heidelberg Retinal Angiograph/OCT; Heidelberg Engineering, Heidelberg, Germany; or OTI Inc, Toronto, Canada) as well as autofluorescence imaging (Heidelberg Retinal Angiograph or Spectralis; Heidelberg Engineering). The outer retinal layer alterations were analyzed in the junctional zone between normal retina and atrophic retina and were correlated with corresponding FAF. Twenty-three eyes of 16 patients between 62 and 96 years of age were examined. There was a significant association between OCT findings and the FAF findings (r = 0.67; P < .0001). Severe alterations of the outer retinal layers at margins on spectral-domain OCT correspond significantly to increased autofluorescence; smooth margins on OCT correspond significantly to normal FAF (kappa, 0.7348; P < .0001). Spectral-domain OCT provides in vivo insight into the pathogenesis of geographic atrophy and its progression. Visualization of reactive changes in the retinal pigment epithelial cells at the junctional zone and correlation with increased FAF; secondary to increased lipofuscin, together these methods may serve as determinants of progression of geographic atrophy.

Morphologic Changes in Patients with Geographic Atrophy Assessed with a Novel Spectral OCT–SLO Combination

To investigate the appearance of geographic atrophy in high-resolution optical coherence tomography (OCT) images, the fundus autofluorescence (FAF) pattern, and infrared images simultaneously recorded with a novel combined OCT-scanning laser ophthalmology (SLO) system. Patients aged over 50 years with geographic atrophy secondary to dry age-related macular degeneration (ARMD) were assessed in a prospective cross-sectional study by means of simultaneous spectral OCT-SLO (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). The integrity of the retinal layers was analyzed in the apparently normal areas, the junctional zone between the normal retina and the geographic atrophy, and the atrophic area. The presence and integrity of the external limiting membrane, the photoreceptor inner segments, the outer segments, and the retinal pigment epithelium were assessed. Fifty-two eyes of 52 patients (28 women, 24 men) aged 51 to 92 years were examined. Retinal layer alterations were documented, not only in atrophic zones, but also in junctional zones surrounding the geographic atrophy. Disintegration of the retinal layers began in the RPE and adjacent retinal layers, such as the photoreceptor inner and outer segments and external limiting membrane. Novel imaging modalities will provide further valuable insight into ARMD pathogenesis. The key to understanding the morphologic change lies in in vivo depiction of retinal layers by spectral OCT technology in combination with other imaging modalities such as FAF.