Retinal Nerve Fiber Research Articles

Optic Disc Features in Pathological Myopia And Myopic Optic Neuropathy

Pathological myopia is defined as excessive axial elongation accompanied by various structural changes in the fundus and optic disc, leading to a decrease in best-corrected visual acuity. Today, with the widespread use of optical coherence tomography (OCT) in ophthalmology, optic disc pathologies have been identified in addition to fundus findings. Due to axial elongation, large optic disc, tilted optic disc, retinal nerve fiber changes, peripapillary atrophy, intachoroidal cavitation and peripapillary-prelaminar schisis are observed. Optic neuropathy occurs in some cases secondary to all these changes occurring in the optic disc. Myopic optic neuropathy can be examined under two headings: glaucomatous/glaucoma-like and nonglaucomatous. In this review, optic disc changes and myopic optic neuropathy, which are important causes of vision loss, are discussed.

Acute Neuro-Retinitis Secondary to a Recently Acquired Ocular Toxoplasmosis in a Young Immunocompetent Patient

A 27-year-old male patient with no medical history presented with a painless unilateral vision loss in the right eye, counting fingers at 5 meters, with active vitreous inflammation, stage II papilledema, whitish lesion on the superior-temporal border of the optic disc and a poor macular reflex, without any active or scarring chorioretinal lesion in the periphery. Multimodal imaging showed intra- and subretinal macular edema with early hypo-fluorescence followed by progressive centripetal filling of the peripapillary lesion and finally papillary diffusion. The visual field revealed an inferotemporal defect. Blood work showed hyperleukocytosis with positive toxoplasma serology, the rest of the workup was negative, especially no immunosuppression. The diagnosis of toxoplasmic anterior optic neuropathy was made due to the papillary and peripapillary involvement without a distant active or scarring lesion, with positive toxoplasma IgG and IgM serology. Trimethoprim/sulfamethoxazole antibiotic treatment with systemic corticosteroid therapy was initiated in our patient with an excellent outcome, including restoration of visual acuity to 10/10, complete vitreous clearance, complete resolution of the papillary and macular edema, and the peripapillary lesion without visible scarring, but leaving a persistent defect of the corresponding retinal nerve fibers. This clinical case thus illustrates a toxoplasmic anterior optic neuropathy with direct papillary involvement complicated by macular edema, a rare and atypical clinical entity of ocular toxoplasmosis, especially in a young immunocompetent subject, reflecting the clinical polymorphism of this pathology.

The effect of transcranial magnetic stimulation on retinal nerve fiber, macular and choroidal thickness in depression

The effect of transcranial magnetic stimulation on retinal nerve fiber, macular and choroidal thickness in depression

Clinical and histological characteristics of axial myopia

Myopic axial elongation is associated with various non‐pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell density and retinal layer thickness, mainly in the retro‐equatorial to equatorial regions; choroidal and scleral thinning pronounced at the posterior pole and least marked at the ora serrata; and a shift in Bruch's membrane opening (BMO) occurring in moderately myopic eyes and typically in the temporal/inferior direction. The BMO shift leads to an overhang of Bruch's membrane (BM) into the nasal intrapapillary compartment and BM absence in the temporal region (i.e., parapapillary gamma zone), optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter, fovea–optic disc distance elongation, reduction in angle kappa, and straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibres. Highly myopic eyes additionally show an enlargement of all layers of the optic nerve canal, elongation and thinning of the lamina cribrosa, peripapillary scleral flange (i.e., parapapillary delta zone) and peripapillary choroidal border tissue, and development of circular parapapillary beta, gamma, and delta zone. Pathological features of high myopia include development of macular linear RPE defects (lacquer cracks), which widen to round RPE defects (patchy atrophies) with central BM defects, macular neovascularization, myopic macular retinoschisis, and glaucomatous/glaucoma‐like and non‐glaucomatous optic neuropathy. BM thickness is unrelated to axial length. Including the change in eye shape from a sphere in emmetropia to a prolate (rotational) ellipsoid in myopia, the features may be explained by a primary BM enlargement in the retro‐equatorial/equatorial region leading to axial elongation.

Two Cases of Sudden Intraocular Pressure Elevation in Children after Steroid Treatment

Purpose: We report two cases of sudden intraocular pressure (IOP) elevation in children after steroid treatment.Case summary: (Case 1) An 8-year-old boy visited the hospital with vomiting and headache that had begun 3 days after application of dexamethasone eyedrops. IOPs were 55 and 62 mmHg in the right and left eyes, respectively; both anterior chambers were normal. The eyedrops were stopped and timolol/dorzolamide was applied twice daily. After intravenous mannitol injection, the IOPs of both eyes decreased to 18 mmHg within 24 hours. (Case 2) A 10-year-old boy diagnosed with coronavirus disease 2019 three days prior had been prescribed methylprednisolone 4 mg twice daily; he visited the hospital with headache, eye pain, and decreased vision that began 1 day after medication. IOPs were 41 and 54 mmHg in the right and left eyes, respectively; both anterior chambers were normal. After drug discontinuation, timolol/dorzolamide, brimonidine, and latanoprost eyedrops were applied. Subsequently, after intravenous mannitol injection, the IOPs decreased within 24 hours to 7 and 16 mmHg in the right and left eyes, respectively; they remained stable. However, thinning was observed in the retinal nerve fiber and ganglion cell-inner plexiform layer.Conclusions: Children can develop rapid IOP elevation after even 1 day of steroid use; residual structural damage may be present, despite prompt treatment. Clinicians must closely monitor such patients for atypical IOP elevation.

Myopia: Histology, clinical features, and potential implications for the etiology of axial elongation.

Myopic axial elongation is associated with various non-pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell density and retinal layer thickness, mainly in the retro-equatorial to equatorial regions; choroidal and scleral thinning pronounced at the posterior pole and least marked at the ora serrata; and a shift in Bruch's membrane opening (BMO) occurring in moderately myopic eyes and typically in the temporal/inferior direction. The BMO shift leads to an overhang of Bruch's membrane (BM) into the nasal intrapapillary compartment and BM absence in the temporal region (i.e., parapapillary gamma zone), optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter, fovea-optic disc distance elongation, reduction in angle kappa, and straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers. Highly myopic eyes additionally show an enlargement of all layers of the optic nerve canal, elongation and thinning of the lamina cribrosa, peripapillary scleral flange (i.e., parapapillary delta zone) and peripapillary choroidal border tissue, and development of circular parapapillary beta, gamma, and delta zone. Pathological features of high myopia include development of macular linear RPE defects (lacquer cracks), which widen to round RPE defects (patchy atrophies) with central BM defects, macular neovascularization, myopic macular retinoschisis, and glaucomatous/glaucoma-like and non-glaucomatous optic neuropathy. BM thickness is unrelated to axial length. Including the change in eye shape from a sphere in emmetropia to a prolate (rotational) ellipsoid in myopia, the features may be explained by a primary BM enlargement in the retro-equatorial/equatorial region leading to axial elongation.

Demographic and Socioeconomic Characteristics of Glaucoma Suspects in a Tertiary Care Center of Pakistan

Purpose: To describe the demographic characteristics of Glaucoma Suspects (GS) presenting to the glaucoma clinic in a tertiary care settings. Study Design: Descriptive observational study. Place & Duration of Study: Glaucoma clinic of Al-Shifa Trust Eye Hospital, Rawalpindi, from September 2015 to February 2016. Methods: Patients attending the glaucoma clinic were examined and intraocular pressure (IOP), iridocorneal angles, anterior and posterior segments evaluation, vertical cup-to-disc ratio (vCDR) were measured. Retinal nerve fiber (RNFL-Global) thickness was calculated by the Optical Coherence tomography machine using software version 6.0.9. Subjects qualifying as glaucoma suspects were interviewed for demographic and systemic conditions. All the information was recorded on a predesigned proforma and descriptive statistics was used for analysis. Results: A total of 876 patients were examined. Eighty-two (9.36%) patients fulfilled the criteria of GS. There were 57.3% females and mean age of sample was 56.78 ± 12.83 (Range 40 – 70 years). Hypertension was found in 34.1% (n = 28) and diabetes in 25.6% (n = 21). Other diseases were asthma, depression, cardiac and gastric problems. Most of the patients belonged to lower or upper lower class, which represents a huge number on socioeconomic status scale. Mean IOP (both eyes) was 13.93 ± 3.23 mmHg (range 6 – 22 mmHg). Only 5% of subjects had vCDR of > 0.8.RNFL-Global of 79 (48.2%) eyes were within normal limits. Conclusions: Majority of GS belong to lower or lower middle socioeconomic class. The health authorities must focus on this issue to provide easily accessible diagnostic facilities for reducing the economic burden of this problem.

Microglia – An innocent bystander?

AbstractUnder normal conditions, microglia act as neuropathology sensors and are neuroprotective.Microglia are spatially organized features as mosaic in the retina; distributed in the plexiform layers of the retina and in the retinal nerve fibre layer‐ganglion cell layer, in order to control the environment and detect changes that can cause neuronal damage. Microglial cells may undergo two different types of activation in response to injuries, being an important player in maintaining retinal balance to a stressful situation. The microglia phenotype called M2‐like, secrete anti‐inflammatory mediators and neurotrophic factors that act as neuroprotectors, while the M1‐like generates a massive inflammatory response, being neurotoxic. When a neurodegenerative process occurs, such as that caused by protein deposits in Alzheimer's Disease (AD), the microglia responds changing its phenotype, which will cause changes in its shape, promoting migration to the area of damage, changing the arrangement in the tissue that gives rise to cells that converge or form barriers, isolating damaged tissue or phagocytizing toxic aggregate proteins and cellular debris.The migratory capacity of the microglia gives it the property of being able to move in its own layer and even between layers, remodelling the retina with areas of clustered cells and other areas with a shortage of cells. These movements lead to structural changes in the layers of the retinal that can be measured, with regions thickened versus other changes thinned over time as the disease progresses. All this changes can be detected by examining the retina in vivo with optical coherence tomography (OCT) in both animal experimental models and human. OCT allows the evaluation of cellular behaviour indirectly in neurodegeneration, in which at first a thickening can be observed that could be associated with protein deposits or cellular changes caused as a result of the inflammatory process, then in more advanced stages the tissue experiences a neurodegeneration, related to a thinning of the retina due to neuronal loss. These changes have been seen that are similar in both the experimental model, as in AD patients.Therefore, the microglia is not an innocent bystander, but a key player, generating changes based on its dual form of activation.

Reticular Pseudodrusen Are Associated With More Advanced Para-Central Photoreceptor Degeneration in Intermediate Age-Related Macular Degeneration.

PurposeThe purpose of this study was to examine retinal topographical differences between intermediate age-related macular degeneration (iAMD) with reticular pseudodrusen (RPD) versus iAMD without RPD, using high-density optical coherence tomography (OCT) cluster analysis.MethodsSingle eyes from 153 individuals (51 with iAMD+RPD, 51 with iAMD, and 51 healthy) were propensity-score matched by age, sex, and refraction. High-density OCT grid-wise (60 × 60 grids, each approximately 0.01 mm2 area) thicknesses were custom-extracted from macular cube scans, then compared between iAMD+RPD and iAMD eyes with correction for confounding factors. These “differences (µm)” were clustered and results de-convoluted to reveal mean difference (95% confidence interval [CI]) and topography of the inner retina (retinal nerve fiber, ganglion cell, inner plexiform, and inner nuclear layers) and outer retina (outer plexiform/Henle's fiber/outer nuclear layers, inner and outer segments, and retinal pigment epithelium-to-Bruch's membrane [RPE-BM]). Differences were also converted to Z-scores using normal data.ResultsIn iAMD+RPD compared to iAMD eyes, the inner retina was thicker (up to +5.89 [95% CI = +2.44 to +9.35] µm, P < 0.0001 to 0.05), the outer para-central retina was thinner (up to −3.21 [95% CI = −5.39 to −1.03] µm, P < 0.01 to 0.001), and the RPE-BM was thicker (+3.38 [95% CI = +1.05 to +5.71] µm, P < 0.05). The majority of effect sizes (Z-scores) were large (−3.13 to +1.91).ConclusionsOCT retinal topography differed across all retinal layers between iAMD eyes with versus without RPD. Greater para-central photoreceptor thinning in RPD eyes was suggestive of more advanced degeneration, whereas the significance of inner retinal thickening was unclear. In the future, quantitative evaluation of photoreceptor thicknesses may help clinicians monitor the potential deleterious effects of RPD on retinal integrity.

Automated screening of glaucoma stages from retinal fundus images using BPS and LBP based GLCM features

AbstractGlaucoma is an eye disease in which the retinal nerve fibers are irreversibly damaged. Early identification of glaucoma is essential because it may slow the progression of the illness. The clinical treatments and medical imaging methods that are currently available are all manual and require expert supervision. An automated glaucoma diagnosis system that is fast, accurate, and helps to reduce the load on professionals is necessary for mass screening. In our proposed work, a novel approach based on bit‐plane slicing (BPS), local binary pattern (LBP), and gray‐level co‐occurrence matrix (GLCM) is used. First, fundus images are separated into channels like red, green, and blue, and these separated channels are split into plans using BPS. Then, LBP images are obtained from selected green channel images. Second, we extract features based on GLCM from LBP images. Finally, using a least‐squares support vector machine classifier, the higher ranked features are employed to classify glaucoma stages. According to the findings of the experiments, our model outperformed state‐of‐the‐art approaches for glaucoma classification. Using 10‐fold cross‐validation, this model achieved an improved classification accuracy of 95.04%, specificity of 96.37%, and sensitivity of 93.77%. We conducted many relative experiments with deep learning and traditional machine learning‐based models to test our proposed methodology. Compared to existing glaucoma classification approaches, the new method has been shown to be more efficient.

Normative data and repeatability for macular ganglion cell layer thickness in healthy Swedish children using swept source optical coherence tomography

BackgroundOptical coherent tomography (OCT) technology is evolving with improved resolution and accuracy in segmentation between different cell layers in the retina. The ganglion cell layer in the macula region is a window to see what is happening in the visual pathways and a macula OCT is an examination that most children tolerate. This makes updated normative data necessary since variables may differ between different OCT devices and normative data for children is often not presented.The aim of this study was to develop normative data for macular ganglion cell layer thickness in children, measured with swept source OCT, and investigate the repeatability between measurements.MethodsHealthy Swedish children between 4 and 16 years old, with normal refraction, spherical equivalent mean:1.13 (sd:0.66) dioptre and normal visual acuity Logmar, mean: 0,015 (sd:0,05), were examined with swept source OCT. Macula OCT was performed three times in both eyes and the different retinal layers were evaluated.ResultsFifty-eight children were screened for inclusion. Fifty-five children were included in the study, 24 boys and 31 girls. Mean age was 8.9 years. Results from right eyes was analysed. The mean average thickness of macular ganglion cell layer thickness, retinal nerve fibre layer/ganglion cell layer boundary to inner plexiform layer/inner nuclear layer boundary, was 68.0 μm (sd:4.0, range:58-77). There was no correlation with sex or age. Fifty-three children manage to complete two, and 41 children three acceptable measurement and the mean coefficient of variation was low.ConclusionThe ganglion cell layer thickness differs according to which OCT device that is used, and the population examined. This makes normative data essential to accurately interpret results. Swept source OCT of the macula have excellent repeatability and the examination well tolerated in most children making it an investigation useful for diagnosing and following diseases in the optic pathways.

Neurodegenerative changes of retina in Parkinson disease

In Parkinson’s disease (PD), some structural changes in the retina have been shown using optical coherence tomography (OCT). Among them most attractive are atrophic changes in retinal nerve fi ber layer (RNFL). However, diagnostic signifi cance of the OCT method in PD remains debatable. Objective: to investigate a thickness of RNFL in Parkinson’s disease patients and to determine the signifi cance of the OCT method in the PD diagnostics. Materials and methods. In PD patients (n = 24) and in a control group (n = 20) OCT was used to study the thickness of RNFL — average, in quadrants and in 10 sectors. Results. In patients with PD thinning of RNFL in the inferior quadrant was revealed (p = 0.009). The sensitivity and specifi city of the method were 56% and 82%, respectively. The thickness of RNFL was not associated with parkinsonian symptoms asymmetry, duration and severity of the disease. In the control group and in PD patients, there was a relationship between the RNFL thickness and age. Conclusion. PD is characterized by atrophic changes in the retina in the form of thinning of RNFL in the inferior quadrant, which confi rms the systemic nature of neurodegenerative pathology in this disease going beyond the substantia nigra and brain tissue. At the same time, the thickness of RNFL showed limited diagnostic value for detecting PD cases.

Visual outcomes after endoscopic pituitary adenomas surgery: our experience

AbstractPurposeTo evaluate visual outcomes after endoscopic pituitary adenoma surgery in patients from Egas Moniz hospital between 2013 and August 2020.MethodsThis is a quantitative, observational, retrospective study. Patients with pituitary adenoma with pre‐ and post‐ surgical visual acuity (LogMAR) and chromatic vision assessment, visual field (Octopus®) testing and optical coherence tomography (Heidelberg®) retinal nerve fibers and macular thickness evaluations were included. Visual parameters were subjected to statistical analysis using SPSS T‐test and Wilcoxon test. A statistically significant p‐value was defined as &lt;0.05.ResultsEighteen patients fulfilled our inclusion criteria. Of the 18 patients, 10 (55.6%) were man, with an average age of 57.4 (±16.5) years old. Fourteen (77.8%) patients had pre‐surgical visual complains for an average of 12.8 (±14.4) months, mostly painless and progressive vision loss 6 (33.3%) and blurred vision 6 (33.3%). Before surgery, most patients (38.9%) already showed contact and opto‐chiasmatic lesion, with an average lesion diameter of 33.1 (±9.2) mm.The most common histological diagnosis was gonadotrophic adenoma (44.4%) with a low mean aggressiveness (Ki 67) of 2.3 (±1.1). Showed statistical significance the difference between the paired samples (pre‐ vs post‐) “opto‐chiasmatic relationship”, “right eye visual acuity”, “right eye visual field mean sensitivity”, “right eye temporal visual field mean sensitivity”, “left eye visual field mean sensitivity”, “left eye temporal mean sensitivity” and “left eye nasal visual field mean sensitivity”. Concerning improvement in tested variables, 11 (68.8%) patients improved in all variables and 14 (82.4%) improved in at least one.ConclusionsOur results go with the current scientific evidence that pituitary adenoma resection in patients with preoperative visual symptoms considerably improve these symptoms.

Retina tissue validation of optical coherence tomography determined outer nuclear layer loss in FTLD-tau

Alzheimer’s disease (AD) is associated with inner retina (nerve fiber and ganglion cell layers) thinning. In contrast, we have seen outer retina thinning driven by photoreceptor outer nuclear layer (ONL) thinning with antemortem optical coherence tomography (OCT) among patients considered to have a frontotemporal degeneration tauopathy (FTLD-Tau). Our objective was to determine if postmortem retinal tissue from FTLD-Tau patients demonstrates ONL loss observed antemortem on OCT. Two probable FTLD-Tau patients that were deeply phenotyped by clinical and genetic testing were imaged with OCT and followed to autopsy. Postmortem brain and retinal tissue were evaluated by a neuropathologist and ocular pathologist, respectively, masked to diagnosis. OCT findings were correlated with retinal histology. The two patients had autopsy-confirmed FTLD-Tau neuropathology and had antemortem OCT measurements showing ONL thinning (66.9 μm, patient #1; 74.9 μm, patient #2) below the 95% confidence interval of normal limits (75.1–120.7 μm) in our healthy control cohort. Postmortem, retinal tissue from both patients demonstrated loss of nuclei in the ONL, matching ONL loss visualized on antemortem OCT. Nuclei counts from each area of ONL loss (2 – 3 nuclei per column) seen in patient eyes were below the 95% confidence interval (4 – 8 nuclei per column for ONL) of 3 normal control retinas analyzed at the same location. Our evaluation of retinal tissue from FTLD-Tau patients confirms ONL loss seen antemortem by OCT. Continued investigation of ONL thinning as a biomarker that may distinguish FTLD-Tau from other dementias is warranted.

Temporal phase evolution OCT for measurement of tissue deformation in the human retina in-vivo

We demonstrate the use of temporal phase evolution (TPE-) OCT methods to evaluate retinal tissue deformation in-vivo over time periods of several seconds. A custom built spectral domain (SD)-OCT system with an integrated retinal tracker, ensuring stable imaging with sub-speckle precision, was used for imaging. TPE-OCT measures and images phase differences between an initial reference B-scan and each of the subsequent B-scans of the evaluated temporal sequence. In order to demonstrate the precision and repeatability of the measurements, retinal nerve fiber (RNF) tissue deformations induced by retinal vessels pulsating with the heartbeat were analyzed in several healthy subjects. We show TPE maps (M-scans of phase evolution as a function of position along B-scan trace vs. time) of wrapped phase data and corresponding deformation maps in selected regions of the RNF layer (RNFL) over the course of several cardiac cycles. A reproducible phase pattern is seen at each heartbeat cycle for all imaged volunteers. RNF tissue deformations near arteries and veins up to ∼ 1.6 µm were obtained with an average precision for a single pixel of about 30 nm. Differences of motion induced by arteries and veins are also investigated.

Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer\u2019s Disease

Retina and optic nerve are sites of extra-cerebral manifestations of Alzheimer’s Disease (AD). Amyloid-β (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau protein are detected in eyes from AD patients and transgenic animals in correlation with inflammation, reduction of synapses, visual deficits, loss of retinal cells and nerve fiber. However, neither the pathological relevance of other post-translational tau modifications—such as truncation with generation of toxic fragments—nor the potential neuroprotective action induced by their in vivo clearance have been investigated in the context of AD retinal degeneration. We have recently developed a monoclonal tau antibody (12A12mAb) which selectively targets the neurotoxic 20–22 kDa NH2-derived peptide generated from pathological truncation at the N-terminal domain of tau without cross-reacting with its full-length normal protein. Previous studies have shown that 12A12mAb, when intravenously (i.v.)-injected into 6-month-old Tg2576 animals, markedly improves their AD-like, behavioural and neuropathological syndrome. By taking advantage of this well-established tau-directed immunization regimen, we found that 12A12mAb administration also exerts a beneficial action on biochemical, morphological and metabolic parameters (i.e. APP/Aβ processing, tau hyperphosphorylation, neuroinflammation, synaptic proteins, microtubule stability, mitochondria-based energy production, neuronal death) associated with ocular injury in the AD phenotype. These findings prospect translational implications in the AD field by: (1) showing for the first time that cleavage of tau takes part in several pathological changes occurring in vivo in affected retinas and vitreous bodies and that its deleterious effects are successfully antagonized by administration of the specific 12A12mAb; (2) shedding further insights on the tight connections between neurosensory retina and brain, in particular following tau-based immunotherapy. In our view, the parallel response we detected in this preclinical animal model, both in the eye and in the hippocampus, following i.v. 12A12mAb injection opens novel diagnostic and therapeutic avenues for the clinical management of cerebral and extracerebral AD signs in human beings.

Automated macular segmentation in compressive optic neuropathy and glaucomatous optic neuropathy

PurposeCompressive optic neuropathy (CON) can sometimes mimic glaucomatous optic neuropathy (GON), leading to inadequate management. Our purpose was to compare the macular area of patients with CON and GON to healthy controls (HC) and to determine if the macula area was able to distinguish between CON and GON.MethodsRetrospective, observational, cross‐sectional study, enrolling 70 patients (22 patients with CON, 25 with GON and 23 HC). Subjects were matched by age (median of 61 [±11.6]), and one eye was randomly selected. Spectral‐domain optical coherence tomography (SD‐OCT) images were generated using the Spectralis® OCT device (Heidelberg, Germany). An automated algorithm was used to segment the macular retina into nine layers and evaluate the thickness of each layer in the foveal, inner, and outer Early Treatment Diabetic Retinopathy Study (ETDRS) subfield rings. Data were compared across all study groups using Kruskal‐Wallis test, followed by pairwise comparisons for each duo. The resulting p‐values were adjusted using the Bonferroni correction and significance level was set at 0.05.ResultsHC had thicker inner retinal layer (IRL) compared with GON and CON (p &lt; 0.05). Global retinal thickness was significantly thinner in the inner superior (IS) and inner nasal (IN) subfields in CON compared with GON (p &lt; 0.05). The IRL is thinner in CON, specifically in the inner and outer nasal subfields, compared to GON. The IN subfield was thinner in the retinal nerve fibre, ganglion cell and inner plexiform layers (IPL) in CON compared with GON (p &lt; 0.05). No differences were found on the inner nuclear, outer plexiform, outer nuclear and outer retinal layers between groups.ConclusionsOur findings suggest that IRL is thinner in both CON and GON, and the IN subfield is specially affected in CON compared with GON. Despite not being our primary outcome, our results suggest that, compared to HC, layer neurodegeneration in both CON and GON affects mainly the inner layers and that does not extend to layers external to IPL. In conclusion, evaluation of the macular segmented layers damage, by SD‐OCT, may be a useful add‐on tool in the differential diagnosis between these two entities, when their manifestations overlap.

Spectral-domain OCT changes in retina and optic nerve in children with hypoxic\u2013ischaemic encephalopathy

PurposeTo evaluate the effect of neonatal hypoxic–ischaemic injury on the retina and the optic nerve and to correlate ocular damage with systemic parameters, laboratory tests, neurological imaging and therapeutic hypothermia at birth.MethodsForty-one children with hypoxic–ischaemic encephalopathy (HIE) at birth (9.09 ± 3.78 years) and a control group of 38 healthy subjects (9.57 ± 3.47 years) were enrolled in a cohort study. The HIE population was divided into three subgroups, based on the degree of encephalopathy according to Sarnat score and the treatment with therapeutic hypothermia (TH): Sarnat score I not treated with hypothermia, Sarnat score II-III treated with TH and Sarnat score II-III not subjected to TH. Total macular thickness, individual retinal layers and peripapillary nerve fibre layer thickness were measured with spectral-domain optical coherence tomography. Clinical data of perinatal period of HIE children were collected: APGAR score, pH and base excess of funiculus blood at birth, apnoea duration, brain ultrasound, cerebral MRI ischaemic lesions and blood chemistry tests.ResultsChildren with Sarnat score I did not show a reduction of peripapillary nerve fibres and ganglion cell layer compared to the control group (p = 0.387, p = 0.316). Peripapillary nerve fibre layer was 109.06 ± 7.79 μm in children with Sarnat score II-III treated with TH, 108.31 ± 7.83 μm in subjects with Sarnat score II-III not subjected to TH and 114.27 ± 6.81 μm in the control group (p = 0.028, p = 0.007). Ganglion cell layer was thinner in children with Sarnat score II-III treated with TH (50.31 ± 5.13 μm) compared to the control group (54.04 ± 2.81 μm) (p = 0.01). Inner retinal layers damage correlated with C-reactive protein and lactate dehydrogenase increase, while higher levels of total bilirubin were protective against retinal impairment (p < 0.05). Cerebral oedema was related to peripapillary nerve fibre layer damage (p = 0.046).ConclusionsThickness reduction of inner retinal layer and peripapillary nerve fibre impairment was related to encephalopathy severity. Ocular damage was associated with inflammation and cerebral oedema following hypoxic–ischaemic damage.

Retinal Tropism and Transduction of Adeno-Associated Virus Varies by Serotype and Route of Delivery (Intravitreal, Subretinal, or Suprachoroidal) in Rats.

Viral-mediated gene augmentation offers tremendous promise for the treatment of inherited retinal diseases. The development of effective gene therapy requires an understanding of the vector's tissue-specific behavior, which may vary depending on serotype, route of delivery, or target species. Using an ex vivo organotypic explant system, we previously demonstrated that retinal tropism and transduction of adeno-associated virus type 2 (AAV2) vary significantly depending on serotype in human eyes. However, the ex vivo system has limited ability to assess route of ocular delivery, and relatively little literature exists on tropic differences between serotypes and routes of delivery in vivo. In this study, we demonstrate that retinal tropism and transduction efficiency of five different AAV2 serotypes (AAV2/1, AAV2/2, AAV2/6, AAV2/8, and AAV2/9) expressing enhanced green fluorescent protein driven by a cytomegalovirus promoter vary greatly depending on serotype and route of delivery (intravitreal, subretinal, or suprachoroidal) in rats. With subretinal delivery, all serotypes successfully transduced the retinal pigmented epithelium and outer nuclear layer (ONL), with AAV2/1 displaying the highest transduction efficiency and AAV2/2 and AAV2/6 showing lower ONL transduction. There was minimal transduction of the inner retina through subretinal delivery for any serotype. Tropism by suprachoroidal delivery mirrored that of subretinal delivery for all AAV serotypes but resulted in a wider distribution and greater ONL transduction. With intravitreal delivery, retinal transduction was seen primarily in the inner retina (retinal nerve fiber, ganglion cell, and inner nuclear layers) for AAV2/1 and AAV2/6, with AAV2/6 showing the highest transduction. When compared with data from human explant models, there are substantial differences in tropism and transduction that are important to consider when using rats as preclinical models for the development of ocular gene therapies for humans.

Involvement of serum anti-retinal antibodies in the pathophysiology of diabetic retinopathy: a pilot study.

The aim of this single-center cross-sectional study was to identify tissue targets for circulating anti-retinal antibodies (ARAs) in the serum of patients with diabetic retinopathy (DR). The study included 61 participants with DR (30 with nonproliferative diabetic retinopathy and 31 with proliferative diabetic retinopathy) and 30 healthy controls. An indirect immunofluorescence (IIF) test was used to detect serum ARAs and identify their targets in the tissue. Four types of ARAs were found in serum samples from DR patients: antibodies against the outer segments of the rods, antibodies against the outer segments of the cones, antibodies against the cytoplasmic components of retinal nuclear layer cells, and antibodies against retinal nerve fibers. A significant difference was noted between groups in the prevalence of antibodies against the outer segments of the rods (NPDR, 40%; PDR, 74.2%; and controls, 40%; P = 0.008) as well as antibodies against the outer segments of the cones (NPDR, 23.3%; PDR, 61.3%; and controls, 30%; P = 0.005). Interestingly, the distribution of immunofluorescence intensity for the outer segments of the rods and cones differed significantly between study groups (P ≢ 0.001 and P = 0.019, respectively). In conclusion, the results of our pilot study showed that in most patients with DR, the outer segments of photoreceptors tend to be the tissue target for serum ARAs. This may indicate their possible involvement in the pathogenesis of DR. However, further research is needed to fully elucidate whether these antibodies participate in photoreceptor damage in the course of DR.