Differences in imaging biomarkers between patients with intermediate and advanced non-neovascular age-related macular degeneration (AMD) in the University of Colorado AMD registry.

PURPOSE: To quantify and compare the different prevalence rates of specific retinal imaging biomarkers in patients with intermediate AMD (iAMD) and advanced non-neovascular AMD (nnAMD). METHODS: Cross-sectional study of patients with iAMD and advanced nnAMD. Imaging studies were reviewed for qualitative imaging biomarkers. Choroidal thickness measurements were obtained subfoveally and in 1000 um and 2000 um intervals away from the fovea. The Chi-squared test and Fisher's exact test were used to compare rates of imaging biomarkers among the two cohorts. P-value of <0.05 was considered significant. RESULTS: 376 eyes of 197 patients with iAMD and 187 eyes of 97 patients with advanced nnAMD were recruited. There were significantly lower rates of the following imaging biomarkers in the iAMD compared with the advanced nnAMD cohorts: soft drusen (66.0% vs. 84.2%, p = 0.001), calcified drusen (4.3% vs. 40.0%, p < 0.0001), RPD (26.2% vs. 53.3%, p < 0.0001), ORT (0.5% vs. 46.9%, p < 0.0001), RP (1.1% vs. 46.3%, p < 0.0001), pigment migration (53.2% vs. 100%, p < 0.0001), and iRORA (17.9% vs. 80.2%, p < 0.0001). In the iAMD cohort, choroidal thickness was significantly greater at 188 µm (SD: 60) and 194 µm (SD: 69), compared to the advanced nnAMD with measurements of 153 µm (SD: 68), and 161 µm (SD: 76). This difference was statistically significant (p < 0.0001 and p = 0.0002). CONCLUSIONS: Our results highlight significant differences in imaging biomarkers between both cohorts. Key biomarkers, such as iRORA, RPD, pigment migration, and thinner choroidal thickness, were associated with advanced nnAMD. Identifying these biomarkers early may help target patients who could benefit from new treatments, potentially delaying vision loss.

Characterization of central-involved diabetic macular edema using OCT and OCTA.

PURPOSE: To characterize the occurrence of diabetic macular edema and the presence of abnormal retinal fluid accumulation in nonproliferative diabetic retinopathy (NPDR). METHODS: In this two-year prospective study, a total of 122 eyes with diabetes type 2 underwent optical coherence tomography (OCT) and OCT-Angiography in association with OCT-Fluid imaging, a novel algorithm of OCT analysis allowing quantification of abnormal accumulation of fluid in the retina through low optical reflectivity ratios (LOR). Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment was performed using 7-field color fundus photography. Best corrected visual acuity was also recorded. RESULTS: During the 2-year follow-up, 23 eyes (19%) developed central-involved diabetic macular edema (CI-DME) and 2 eyes (2%) developed clinically significant macular edema (CSME). In the two-year period of the study, eyes that developed CI-DME showed a progressive increase in central retinal thickness (CRT) (ß = 7.7 ± 2.1 µm/year, p < 0.001) and in LOR values (ß = 0.009 ± 0.004 ratio/year, p = 0.027). The increase in CRT and abnormal retinal fluid, represented by increased LOR ratios, are associated with increased retinal perfusion in the deep capillary plexus (DCP) (skeletonized vessel density, p = 0.039). In contrast, the eyes with CSME showed decreased retinal perfusion and abnormal fluid located in the outer layers of the retina. CONCLUSIONS: CI-DME and CSME appear to represent different entities. Eyes with CI-DME show increases in abnormal retinal fluid associated with increased retinal vascular perfusion in the DCP. Eyes with CSME are apparently associated with decreased retinal vascular perfusion in the DCP and abnormal fluid in the outer retina.

Design of a new 3D printed all-in-one magnetic smartphone adapter for fundus and anterior segment imaging.

PURPOSE: To describe and validate a 3D-printed adapter tool which could be used with either a slit lamp or a condensing lens, interchangeable between devices through magnetic fastening, in order to provide physicians a quick, easy and effective method of obtaining clinical photos. MATERIALS AND METHODS: Three specialists, with at least 4-year experience in ophthalmology, gave a rate of image quality obtained by our device and the diagnostic confidence grade. The 3 specialists conducted each 13 or 14 examinations with the smartphone and magnetic adapter. At the end of evaluation, they rated with the Likert scale the ease of use of the device in obtaining clinical images of the anterior segment and ocular fundus respectively. RESULTS: Data of quality perception and confidence demonstrated high values not dissimilar to the "de visu" eye examination. Moreover the instrument we designed turned out to be very user friendly. CONCLUSION: Our adapter coupled with a modern smartphone was able to obtain 4k images and videos of anterior segment, central and peripheral fundus, in an easy and inexpensive way.

No side effects on rabbit retina or vitreous microenvironment by nd:YAG laser vitreolysis.

BACKGROUND: To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous cytokines in the rabbits. METHODS: Nine male New Zealand rabbits underwent Nd:YAG laser vitreolysis of 10 mJ x 500 pulses in the left eyes, while the right eyes were used as controls. Intraocular pressure, color fundus photography, and ultrasound B scan were measured before, as well as 1 day, 4 weeks, and 12 weeks after Nd:YAG laser vitreolysis. Three rabbits were euthanized 1 day, 4 weeks, and 12 weeks after treatment, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and hematoxylin-eosin (H&E) staining were used to look for pathological changes in the retina. An enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of vascular endothelial growth factor (VEGF) and some inflammatory cytokines, including interferon inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interlenkin 6 (IL-6) in the vitreous humor. The ascorbic acid (AsA) and total reactive antioxidant potential (TRAP) in the vitreous humor were also measured. RESULTS: Following Nd:YAG laser vitreolysis, the levels of VEGF, IP-10, MCP-1, IL6, AsA, and TRAP in the vitreous humor did not change substantially (P > 0.05). There were no detectable pathological changes in the retinal tissues, and no apoptotic signal was found. CONCLUSIONS: Rabbits tolerate Nd:YAG laser vitreolysis without observable impact on retinal tissue or the microenvironment of the vitreous.

Shaking Up Our Approach: The Need for Characterization and Optimization of Pre-clinical Models of Infant Abusive Head Trauma.

Traumatic brain injuries (TBIs) are a large societal and individual burden. In the first year of life, the vast majority of these injuries are the result of inflicted abusive events by a trusted caregiver. Abusive head trauma (AHT) in infants, formerly known as shaken baby syndrome, is the leading cause of inflicted mortality and morbidity in this population. In this review we address clinical diagnosis, symptoms, prognosis, and neuropathology of AHT, emphasizing the burden of repetitive AHT. Next, we consider existing animal models of AHT, and we evaluate key features of an ideal model, highlighting important developmental milestones in children most vulnerable to AHT. We draw on insights from other injury models, such as repetitive, mild TBIs (RmTBIs), post-traumatic epilepsy (PTE), hypoxic-ischemic injuries, and maternal neglect, to speculate on key knowledge gaps and underline important new opportunities in pre-clinical AHT research. Finally, potential treatment options to facilitate healthy development in children following an AHT are considered. Together, this review aims to drive the field toward optimized, well-characterized animal models of AHT, which will allow for greater insight into the underlying neuropathological and neurobehavioral consequences of AHT.

Usefulness of Schirmer's tear strips and borosilicate glass tubes in chemical analysis of human tear fluid: A practical check in VEGF detection.

INTRODUCTION: Human tears contain a number of agents which may play an important role in diagnosing local eye disorders as well as systemic diseases. The small amount of fluid obtained during the collection and the consequent difficulty in analysing it are the main problems encountered in the diagnostic process. AIM: We decided to investigate the practical usefulness of two simple methods of collecting tear fluid for chemical analysis, i.e., glass tubes and Schirmer's strips. The substance analyzed was vascular endothelial growth factor (VEGF), a compound commonly recognized in ophthalmology. METHODS: We used standard Schirmer's tear test and calibrated glass tubes for tear fluid collection in healthy volunteers. The standard ELISA assay was used to check the effectiveness of the tear sampling by estimating the VEGF level. RESULTS: The results of the study show that Schirmer's tear strip test is a more effective tool of the two. Moreover, using Schirmer's strips to obtain tear fluid was found to be more patient friendly and amounts of the tear fluid collected with that test were enough and better for the VEGF detection. CONCLUSIONS: Our study indicates that the widely used Schirmer tear test may be the best method of tear collection for chemical analysis. However, further studies on test calibration are needed.

Evaluation of retinal and choroidal vascular structures in patients with anxiety disorder.

PURPOSE: To evaluate the retinal and choroidal vascular structures in patients with anxiety disorders. METHODS: Thirthy-four eyes of 34 patients who were diagnosed with any anxiety disorders were compared with 32 eyes of 32 age- and sex-matched controls. Central macular thickness (CMT), foveal vascular zone (FAZ) area, total retinal vascular densities of superficial and deep capillary plexus (VDSCP, VDDCP), outer retinal and choriocapillary layers (ORL, CCL) blood flow rates, central subfoveal choroidal thickness (SFCT) and choriodal vascularity index (CVI) were evaluated with optical coherence tomography angiography (OCT-A) and enhanced depth imaging optical coherence tomography (EDI-OCT). RESULTS: No statistical differences were found between the study and control groups in terms of CMT, FAZ area, VDSCP, VDDCP, ORL and CCL blood flow rates. The mean SFCT was 346.26 ± 64.26 µm in patients with anxiety disorder and was found to be statistically significantly thicker than the control group (319.56 ± 37.19 µm) (p = 0.042). Besides, CVI was significantly lower in the study group (71.09 ± 2.64 vs 73.13 ± 3.31, p = 0.008). CONCLUSION: In people with anxiety disorders, the SFCT was found to be thicker and CVI was found to be lower than normal subjects. Although anxiety and stress are important factors in central serous chorioretinopathy, multifactorial factors, including ocular factors, play a role in the pathophysiology of the disease. There is a need for prospective studies with larger series on the subject.

Prevalence of strabismus in premature infants in an age-related perspective.

THE AIM: was to investigate the prevalence of strabismus in premature infants; to identify diagnostic indicators for predicting strabismus at the age of 3-8 years. METHODS: The material was the data of 84 premature infants who underwent ophthalmological examination at the age of 6 months - 3 years and again - at 3-8 years. All children underwent ophthalmic examination for retinopathy of prematurity (ROP) in infancy. RESULTS: An increase in the frequency of strabismus occurrence among preterm infants was observed in 3-8 years compared to the data from 6 months - 3 years - from 13.3% to 20.0% in children without ROP, from 5.9% to 23.5% in children with self-resolving ROP, from 22.7% to 45.5% in children with ROP after laser retinal photocoagulation. The presence of strabismus and structural changes of eye at ages 6 months - 3 years increase the risk of strabismus at ages 3-8 years, OR = 6.5 (95% CI 3.8-11.3), (p < 0.001); OR = 4.2 (95% CI 2.8-6.2), (p = 0.005). The increase in the risk of developing strabismus at ages 3-8 years is associated with the presence of anisometropia, (p = 0.047), amblyopia, (p < 0.05). Children with higher visual acuity at ages 3-8 years have a decreased risk of strabismus, (p < 0.05). CONCLUSIONS: The frequency of strabismus occurrence among preterm infants has increased by ages 3-8 years. Strabismus, structural changes of eye at ages 6 months - 3 years increases the risk of strabismus at ages 3-8 years. Anisometropia and amblyopia increase in the risk of strabismus, higher visual acuity decreases risk of strabismus.

Clinical and multimodal imaging findings in a case of serous maculopathy with absence of retinal pigment epithelium (SMARPE).

INTRODUCTION: The differential diagnosis for serous SRF can involve diseases with widely different pathogenic mechanisms that can range from vascular ocular diseases to ocular tumours and paraneoplastic syndromes. Recently, van Dijk et al. have described in three patients a new entity which they have called serous maculopathy with an absence of retinal pigment epithelium (SMARPE). We hereby describe a case of this infrequent macular disease and report its characteristic findings on multimodal imaging. CASE DESCRIPTION: We present the case of a 65-year-old hyperopic woman with a three-year history of visual acuity (VA) loss in her left eye. Prior optical coherence tomography (OCT) had revealed the presence of serous subretinal fluid that had shown no response to treatment with intravitreal injections. On swept source OCT angiography scan, no macular alterations in the retinal vascular plexus structure were noted and there was no evidence of choroidal neovascularization. Ultra-widefield fluorescence angiography of the left eye revealed an early hyperfluorescent macular spot corresponding to the area of absent RPE and late fluorescein pooling. On ultra-widefield indocyanine green angiography there were no central or peripheral abnormalities of choroidal vascularization. CONCLUSION: This recently described entity should be considered as a differential diagnosis in persistent serous subretinal fluid. Multimodal imaging helps differentiate SMARPE from its main differential diagnoses, and care should be taken to identify and differentiate it from similar conditions to avoid unnecessary treatment with its possible side effects and complications.

Long-term complications according to silicone oil type. A single center cohort study.

PURPOSE: To study the incidence of macular edema (ME), ocular hypertension (OHT), emulsification and migration to the anterior chamber (AC) of silicone oil (SO) in patients after complex retina surgery, stratified by SO type. METHODS: Retrospective, cohort study. Patients who underwent retina surgery with SO injection and extraction in our center were included. We compared the complication rates of ME, OHT, emulsification and migration to the AS according to SO type (1300cSt, 5700cSt and heavy SO). Data on age, sex, emulsification time, duration of the tamponade, previous retina surgeries and diagnosis were also gathered and included in a multivariate analysis. RESULTS: We included 163 patients (mean age of 64.8 years; mean duration of the tamponade: 11 months). Rates of emulsification, ME, OHT and SO migration to the AC were similar in all groups (p = 0.998, 0.668, 0.915 and 0.360). ME was the most frequent complication (33.3-47.8%), which resolved after SO extraction in 77.6% of cases. The majority of cases with OHT persisted (61.7%). Emulsification was related to younger age (OR 0.94) and longer duration of the tamponade (OR 1.04). The odds of SO migration to the AC increased with emulsification (OR 2.78), recurrent retinal detachment (OR 0.99) and aphakia (OR 4.05). CONCLUSIONS: We propose SO extraction as the preferred treatment for ME during SO tamponade. SO extraction should be performed sooner in younger patients to avoid emulsification. In selected patients, we suggest a longer duration of the tamponade up to 11 months with a reasonable safety profile, regardless of the SO type.

A Brazilian case of exudative perifoveal vascular anomalous complex responsive to aflibercept intravitreal injections.

PURPOSE: To report a case of exudative perifoveal exudative vascular anomalous complex (ePVAC) in a Brazilian healthy patient that underwent a complete resolution after aflibercept intravitreal injections. CASE DESCRIPTION: A 41-year-old healthy Brazilian man complained of acute central vision loss in his right eye (RE). Fundus examination showed a perifoveal hemorrhagic aneurysmal lesion, accompanied by several hard exudates in RE. On fluorescein angiography, these abnormalities showed a progressive hyperfluorescence with surrounding leakage. Optical coherence tomography (OCT) revealed a deep, perifoveal hyporeflective cystic space with a hyperreflective wall and hyperreflective material inside of fibrin-like aspect. Around this aneurism, intraretinal hyporeflective spaces suggestive of exudation were detected. Nor pathological flow signal, or telangiectatic dilations were evidenced on OCT-angiography. Therefore, a diagnosis of exudative ePVAC in RE was hypothesized. After an initial observation, the patient underwent three monthly aflibercept intravitreal injections (0.05 ml/2 mg), with a significative anatomical and functional improvement after two weeks from first dose. On last follow-up at five months from baseline, patient experienced no evidence of new exudation and a stable visual acuity. DISCUSSION: Placental growth factor (PlGF) may impact on pericytes' dropout, and thus on ePVAC development. In contrast to the other anti-VEGF drugs, aflibercept is the only molecule contrasting PlGF. Therefore, aflibercept would act on ePVAC not as an anti-VEGF drug, but rather as an anti-PlGF one. CONCLUSION: This report encouraged the use of aflibercept as a therapeutic option for ePVAC. Further studies are required to confirm our result and the impact of PlGF on ePVAC pathogenesis.

OCT-angiography in optic disk pit after inverted ILM flap: A case report.

BACKGROUND: To describe OCT-angiography features in a case of an optic disk pit (ODP) which underwent a pars plana vitrectomy with inverted ILM flap for macular detachment. CASE PRESENTATION: A 12 years old child with an ODP responsible for a macular detachment underwent 23G vitrectomy in the subacute phase of the disease with an inverted ILM flap used as a plug over the lateral dehiscence of the pit. Among the various retinal imaging examinations performed in the post-operative period, the OCT-angiography showed very interesting features characterized by a capillary drop-out in correspondence of the superficial and deep capillary plexus, a fine texture of the choroid capillary layer and star-shaped folds in correspondence of both the outer retina and the choroid capillary layer. OCT-A performed 24 months after surgery showed a normalization of the macular perfusion which correlated with a full recovery of the visual acuity of the young child. CONCLUSIONS: OCT-A is an useful tool to monitor the subretinal fluid reabsorption after ILM inverted flap surgery for ODP-maculopathy and correlates with visual function. OCT-A may be useful in the follow-up of this rare condition as well as its response to therapeutic strategies.

Association Between Retinal Pathology and Hearing in Older Adults.

We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology. Data from 536 older adults from the National Health and Nutritional Examination Survey 2005 to 2006 including sociodemographic and health characteristics, pure-tone hearing thresholds, and retinal pathologies were collected and analyzed. Associations between retinal and hearing pathologies were modeled with multivariable-adjusted linear regressions. 75% of participants had hearing loss and 15% of participants had retinopathy. The association between retinopathy, microaneurysms, and blot hemorrhages with better speech-frequency pure tone average was -2.81 (95% confidence interval [CI]: -5.72 to 0.10), -4.75 (95% CI: -8.73 to -0.78), and -5.34 (95% CI: -8.68 to -2.00), respectively. The presence of retinopathy, microaneurysms, and blot hemorrhages was inversely associated with hearing loss. Further studies are needed to better understand the potential relationship between microvascular pathologies of the eye and ear.

Correlation between retinal sensitivity and retinal vascular perfusion after idiopathic epiretinal membrane peeling.

BACKGROUND: To evaluate the correlations between anatomical and functional changes after idiopathic epiretinal membrane (iERM) surgery. METHODS: In this prospective, observational, single-center study, consecutive patients who underwent iERM peeling were enrolled. Reported data were pre- and postoperative best-corrected visual acuity (BCVA), retinal sensitivity (RS) and fixation stability values on microperimetry, structural macular features on SD-OCT and OCTA. RS of foveal and parafoveal area was analysed and two sub-groups were identified whether RS improved or remained unchanged/worsened after surgery; consequently, vascular perfusion density (VPD) of the same area was studied. RESULTS: Twenty-nine eyes of 29 patients were examined. The post-operative improvement in terms of BCVA, RS and fixation within the central 4 degrees was significant (p < 0.001, p < 0.001, p = 0.001), as well as the foveal thickness and macular volume change/reduction (p < 0.001). The pre-operative superficial VPD, choriocapillaris VPD and capillary free zone (CFZ) area were significantly reduced compared to the fellow healthy eye (p = 0.001, p = 0.02, p < 0.001). Choriocapillaris VPD showed a statistically significant increase after surgery (p < 0.02). Superficial, deep and choriocapillaris VPD of the improved RS group showed a significant increase both in foveal (p = 0.03, p = 0.03, p = 0.01) and parafoveal areas (p = 0.01, p = 0.03, p = 0.001). CONCLUSIONS: We reported a higher VPD in the retinal area that experienced a retinal sensitivity improvement 6 months after ERM surgery. This result objectifies the tight bond between visual function and retinal perfusion in ERM patients.

Branch retinal artery occlusion with unruptured retinal arterial macroaneurysm post-SARS-CoV-2 vaccination: A case report.

INTRODUCTION: Many adverse occurrences in the eye have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. This is the first report of a patient with an unruptured retinal arterial macroaneurysm (RAM) who developed branch retinal artery occlusion (BRAO) one day after SARS-CoV-2 vaccination (BNT162b2 by Pfizer-BioNTech). PATIENT REPORT: A 75-year-old man with a pertinent history of type-2 diabetes mellitus visited the hospital complaining of sudden visual loss in his right eye 1 day after receiving the fourth dose of the SARS-CoV-2 mRNA vaccine; his best-corrected visual acuity (BCVA) decreased from 1.0 to 0.7 (Snellen decimal). The patient had previously been diagnosed with an unruptured RAM and superior paracentral acute middle maculopathy in the same eye. Fundus examination showed increased sheathing of blood vessels. Indocyanine green showed a hyperfluorescent area suggestive of RAM on the right eye disc. Fluorescein angiography and optical coherence tomography angiography revealed arterial obstruction findings in the upper retinal area. DIAGNOSIS AND INTERVENTION: The patient was diagnosed with BRAO with RAM and was followed up without any additional treatment. Follow-up examination after 4 months did not show any improvement in BCVA value. CONCLUSION: This case suggested that BRAO could develop after SARS-CoV-2 vaccination in patients with unruptured RAM; however, more research is required to investigate the causes.

Branch retinal artery occlusion with paracentral acute middle maculopathy related to a COVID-19 infection in a patient with Anosmia.

PURPOSE: To report a case of paracentral acute middle maculopathy (PAMM) due to branch retinal artery occlusion (BRAO) as a complication of COVID-19. METHODS: A case report evaluated through spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, and OCT angiography. RESULTS: A 55-year-old man complained of blurred vision in the right eye. He presented with anosmia and tested positive for COVID-19 one week before. Fundus examination revealed a superior temporal whitening of the retina, SD-OCT showed a hyperreflective band-like lesion on the nuclear layer consistent with PAMM. CONCLUSION: COVID-19 infection involves inflammatory and thrombotic events. Even patients with just anosmia may have complications such as BRAO associated with PAMM.

The contribution of indocyanine green angiography in a case of unilateral retinal pigment epithelium dysgenesis.

PURPOSE: To further enhance understanding of the expanded clinical spectrum of unilateral retinal pigment epithelium dysgenesis (URPED) via numerous imaging modalities including novel markers of highly detailed indocyanine green angiography (ICGA) features. METHODS: Retrospective, observational, case report. RESULTS: URPED in this patient is expressed as a solitary, flat and pigmented lesion in the posterior pole with RPE hyperplasia and atrophic changes. An epiretinal membrane (ERM) causing fine, tortuous retinal vessels and retinal folds was observed. Green and blue excitation light fundus autofluorescence showed a biphasic appearance with hypoautofluorescent rounded lesions and a reticular configuration of normal RPE. Fundus fluorescein angiography revealed diffuse hypofluorescence and hyperfluorescent wisps of leakage in late-phases. Early-phase of ICGA evidenced diffuse hypocianescence and a delineated hypercianescent scalloped margin appeared in the late-phase, together with focal hypocianescent spots. SD-OCT demonstrated irregularity of the RPE with fibrosis and hyperplastic changes combined with atrophic areas. Flat RPE detachments intermingled with healthy-appearing RPE were also observed together with thinning of the outer retina. ERM with thickening and disorganization involving the whole retina was present. Optical coherence tomography angiography (14 × 14 mm) revealed an oval shape foveal avascular zone and vascular anomalies such as tortuosity and looping. CONCLUSION: URPED is an extremely rare clinical entity with only a few cases reported. In this case the almost pathognomonic differential features of URPED were best appreciated with ICGA imaging. To our knowledge, this is the first reported case of URPED with these abnormal findings on ICGA meaning it could be part of the spectrum of the disease.

Retinal neurodegeneration in age-related macular degeneration.

Age-related macular degeneration (AMD) is a complex and multifactorial disease characterized by the damage of the unit comprised of the photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. Although the outer retina appears to be mainly affected in this disorder, several evidences exhibit that also the inner retina may be impaired. In this review we will provide a description of the prominent histologic and imaging findings suggesting an inner retinal loss in these eyes. In details, structural optical coherence tomography (OCT) technology proved either the inner and outer retina is impacted by AMD and that these two impairments are associated. Therefore, the purpose of this review is to provide a description of the role of neurodegeneration in AMD in order to better understand the relationship between neuronal loss and the outer retinal damage in this disease.

NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment.

The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis. Ocular findings in patients with NIID were studied using fundus photographs, optical coherence tomographic images (OCT), and full-field electroretinograms (ERGs). The histopathology of the retina was studied on autopsy samples from two cases with immunohistochemistry. All patients had an expansion of the GGC repeat (87-134 repeats) in the NOTCH2NLC. Two patients were legally blind and had been diagnosed with retinitis pigmentosa prior to the diagnosis of NIID and assessed with whole exome sequencing to rule out comorbidity with other retinal diseases. Fundus photographs around the posterior pole showed chorioretinal atrophy in the peripapillary regions. OCT showed thinning of the retina. ERGs showed various abnormalities in cases. The histopathology of autopsy samples showed diffusely scattered intranuclear inclusions throughout the retina from the retinal pigment epithelium to the ganglion cell layer, and optic nerve glial cells. And severe gliosis was observed in retina and optic nerve. The NOTCH2NLC GGC repeat expansion causes numerous intranuclear inclusions in the retina and optic nerve cells and gliosis. Visual dysfunction could be the first sign of NIID. We should consider NIID as one of the causes of retinal dystrophy and investigate the GGC repeat expansion in NOTCH2NLC.