Imagen en retromodo para el diagnóstico de drusas del disco óptico: una serie de casos / Retro-mode imaging for the diagnosis of optic disc drusen: A case series

Objetivo: Nuestro principal objetivo es el de comparar la capacidad para detectar las drusas del disco óptico (DDO) utilizando diversas técnicas de imágenes no-invasivas, incluida la novedosa técnica de imagen de retromodo (RMI). Como segundo objetivo analizamos las características morfológicas de las DDO bajo esta última técnica. Materiales y métodos: Este estudio incluyó un total de 7 pacientes con DDO bilaterales, obteniendo un total de 14 ojos analizados. Se utilizaron técnicas no invasivas de imágenes multimodales, que incluyeron fotografía multicolor del fondo de ojo (MC), reflectancia en infrarrojo (NIR), autofluorescencia en luz verde y en luz azul (G-FAF y B-FAF, respectivamente) y RMI. La FAF se utilizó como el método principal para el diagnóstico de DDO. Dos observadores realizaron las comparaciones, obteniendo las tasas de detección de cada uno de los métodos. Las mediciones cuantitativas de las DDO incluyeron el número, el perímetro (P) y el área (A) de las DDO identificadas mediante la técnica de RMI. Resultado: La edad promedio de los pacientes incluidos fue de 49,28±23,16 años; 5 de los 7 pacientes fueron de sexo masculino. La técnica de RMI pudo detectar DDO en todos los casos, con una sensibilidad del 100%, en comparación con MC (sensibilidad del 60,71%), NIR (sensibilidad del 60,71%), B-FAF (sensibilidad del 100%), G-FAF (sensibilidad del 100%). RMI fue la única técnica de imagen capaz de evaluar morfológica y cuantitativamente las DDO. Conclusiones: RMI es una prometedora modalidad no-invasiva de imagen para diagnosticar DDO superficiales, proporcionando información valiosa sobre la distribución, la ubicación y el tamaño de estas. Por lo tanto, mediante nuestros resultados sugerimos la incorporación de la novedosa técnica de RMI como una herramienta complementaria para el diagnóstico y el seguimiento de DDO en combinación con los otros métodos de imagen multimodales.(AU)

Objective: We aimed to compare the detectability of optic disc drusen (ODD), using various non-invasive imaging techniques, including the novel retro-mode imaging (RMI), as well as to analyze the morphological characteristics of ODD on RMI. Methods: This study involved 7 patients with bilateral ODD, totaling 14 eyes. Multimodal imaging techniques, including multicolor fundus photography (MC), near-infrared reflectance (NIR), green and blue light fundus autofluorescence (G-FAF and B-FAF, respectively), and RMI were used to examine the eyes. FAF was used as the primary method of identifying ODD, and each method's detection rate was compared by two observers. Quantitative measurements of ODD included the number of ODD visualized by the RMI technique, the perimeter (P) and area (A) of ODD were identified. Results: The average age of the patients included was 49.28±23.16 years, with 5 of the 7 being men. RMI was able to detect ODD in all cases, with a sensitivity of 100%, compared to MC (sensitivity 60.71%), NIR (sensitivity 60.71%), B-FAF (sensitivity 100%), G-FAF (sensitivity 100%). RMI was the only imaging technique capable of assessing ODD morphology and quantifying ODD. Conclusions: RMI is a promising imaging modality for diagnosing superficial ODD, providing valuable information on the distribution, location, and size of ODD. We suggest the incorporation of RMI as a complementary tool for diagnosing and monitoring ODD in combination with other multimodal imaging methods.(AU)

Longitudinal changes in optic disc cupping from the baseline in chiasmal lesion optic neuropathy and glaucoma.

We aimed to investigate the changes in cupping in chiasmal lesion optic neuropathy (chON) compared to baseline optic disc and glaucoma. We used a novel study design to enroll patients who had fundus photographs incidentally taken during routine health check-ups prior to the onset of optic neuropathy. In 31 eyes (21 patients) with chON and 33 eyes (30 patients) with glaucoma, we investigated the change in cup-to-disc (C/D) area from the baseline to overt cupping using flicker analysis. Compared to the baseline, 23 eyes (74.2%) had increased cup size and 3 (9.7%) had vascular configuration changes in the chONgroup; in contrast, all glaucoma eyes exhibited changes in cup size and vascular configuration. The increase in C/D area ratio was significantly smaller in chON (0.04 ± 0.04) compared to glaucoma (0.10 ± 0.04, P < 0.001); the minimum residual neuroretinal rim width showed a more pronounced difference (29.7 ± 8.2% vs 7.1 ± 3.9%, P < 0.001). The changes distributed predominantly towards the nasal direction in chON, contrasting the changes to the arcuate fibers in glaucoma. In conclusion, our results provide the first longitudinal evidence of true pathological cupping in chONcompared to photographically disease-free baseline. The marked difference in the residual minimum rim width reaffirms the importance of rim obliteration in the differential diagnosis between the two diseases.

Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review).

Glaucoma is a group of progressive optic nerve disorders characterized by the loss of retinal ganglion cells, a thinner retinal nerve fibre layer and cupping of the optic disk. Apoptosis is a physiological cell death process regulated by genes and plays a crucial role in maintaining tissue homeostasis, ensuring the natural development and immune defence of organisms. Apoptosis has been associated with glaucoma and inhibiting apoptosis by activating phosphatidylinositol 3-kinase­protein kinase B or other medicines can rescue pathological changes in glaucoma. Due to the complex crosstalk of apoptosis pathways, the pathophysiological mechanism of apoptosis in glaucoma needs to be fully elucidated. The present review aimed to discuss the mechanism of cell apoptosis in glaucoma, improve the understanding of the pathophysiology of glaucoma, summarize new directions for the treatment of glaucoma and lay the foundation for new treatment strategies for glaucoma.

Effect of Bergmeister papilla on disc parameters in spectral domain optical coherence tomography.

OBJECTIVES: To investigate the morphological characteristics of Bergmeister papilla (BMP), a persistent hyaloid remnant tissue, and its effects on the measurements and repeatability of spectral-domain optical coherence tomography (OCT). SUBJECTS/METHODS: The subjects of this prospective cross-sectional study including 83 patients with BMP and 76 unaffected individuals, all had open-angle structures. Images, including a 5-line raster and three consecutive optic disc cube scans centred on the optic disc, were acquired using the Cirrus high-definition OCT. BMP's structural characteristics were classified based on the raster scan images, and repeatability of acquiring optic nerve head and retinal nerve fibre layer parameters acquisition was analysed by calculating the test-retest standard deviation (Sw), coefficient of variance (CV), and intraclass correlation coefficient. RESULTS: BMPs (n = 83) were categorised into lifting edge (LE) type (63.9%, n = 53), which partially covers the edge of the optic nerve head, and covering disc (CD) type (36.1%, n = 30), which completely covers the cupping area like a cap. The average cup-to-disc ratio (0.58 ± 0.21), vertical cup-to-disc ratio (0.55 ± 0.21), and cup volume (0.22 ± 0.22) of the CD type were lower than those of the LE type (0.66 ± 0.13, 0.64 ± 0.13, and 0.4 ± 0.27, respectively; all P < 0.05). Tolerability indices for repeatability of cup volume (Sw = 0.40 and CV = 0.36) and inferonasal (4 o'clock) retinal nerve fibre layer (Sw = 0.27 and CV = 0.25) in LE-type BMPs exceeded the cut-off value (0.22) and demonstrated stronger correlation with BMP location than that of the controls. CONCLUSION: Caution should be exercised when interpreting OCT findings in eyes with BMP, as BMP can introduce a pitfall in OCT imaging.

Artificial intelligence in glaucoma detection using color fundus photographs.

PURPOSE: To explore the potential of artificial intelligence (AI) for glaucoma detection using deep learning algorithm and evaluate its accuracy for image classification of glaucomatous optic neuropathy (GON) from color fundus photographs. METHODS: A total of 1375 color fundus photographs, 735 normal optic nerve head and 640 GON, were uploaded on the AI software for training, validation, and testing using deep learning model, which is based on Residual Network (Res Net) 50V2. For initial training and validation, 400 fundus images (200 normal and 200 GON) were uploaded and for the final training and testing 975 (535 normal and 440 GON) were uploaded later. Accuracy, sensitivity, and specificity were used to evaluate the image classification performance of the algorithm. Also, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated. RESULTS: The model used in the study showed an image classification accuracy of 81.3%, sensitivity of 83%, and specificity of 80% for the detection of GON. The false-negative grading was 17% and false-positive grading was 20% for the image classification of GON. Coexistence of glaucoma in patients with high myopia, early glaucoma in a small disc, and software misclassification of GON were the reasons for false-negative results. Physiological large cupping in a large disc, myopic or titled disc, and software misclassification of normal optic disc were the reasons for false-positive results. CONCLUSION: The model employed in this study achieved a good accuracy, and hence has a good potential in detection of GON using color fundus photographs.

[The effect of keratoconus-associated refractive errors on the results of tomographic methods of studying the posterior structures of the eye]. / Vliyanie opticheskikh narushenii pri keratokonuse na rezul'taty tomograficheskikh metodov issledovaniya struktur zadnego segmenta glaza.

PURPOSE: The study assesses the potential influence of refractive errors in keratoconus (KC) on the results of tomographic methods of studying the structures of the posterior eye segment. MATERIAL AND METHODS: The study included 30 patients with bilateral stabilized KC of stages I-IV in classification by M. Amsler. Spherical and cylindrical components of refractions were determined using automatic refractometry, keratometry measurements - based on scanning keratotopography with Scheimpflug analyzer. Aberrometry was performed to evaluate corneal wave front according to the following parameters: root mean square for lower order aberrations (RMS LOA), root mean square for higher order aberrations (RMS HOA), vertical trefoil, vertical coma, horizontal coma and spherical aberrations. Optical coherence tomography (OCT) and laser confocal scanning ophthalmoscopy (HRT 3) data was used in morphometric analysis of the optic nerve head and peripapillary retina. The following morphometric parameters were analyzed: optic nerve head (ONH) area, optic disc cup area, optic disc cup volume, ratio of optic disc cup area to ONH area, neuroretinal rim area, neuroretinal rim volume, peripapillary retinal nerve fiber layer (RNFL) thickness. All studies were performed first without correction, and 30 minutes after installing customized scleral hard contact lenses (SHCL). RESULTS: Compensation of the refractive errors characteristic for KC was achieved as expected with contact correction. OCT revealed a general trend for reduction in the area and volume of the optic disc cupping, ratio of area to volume of the optic disc cupping, as well as an increase in other parameters. As such, with correction the values for area and volume of the neuroretinal rim according to OCT were 2.2 and 13%, HRT 3 - 18 and 51.6%; comparable increase in mean RNFL thickness - 2.8 and 28.5%, respectively (p<0.001). According to HRT 3 data, the area and volume of optic disc cupping statistically significantly decreased (by 21 and 28%, respectively), while OCT showed statistically significant decrease only in cupping area (by 5.7%). The ratio of cupping to ONH area decreased by 6.6 and 23% relative to the initial data obtained with OCT and HRT 3, respectively. Significant decrease in ONH area amid SHCL correction was observed only with HRT 3. The revealed changes in morphometric parameters were analyzed using the fundamental principles of physiological optics. Changes in interference pattern and, consequently, morphometric parameters of structures of the eye fundus in KC are of multifactorial nature, and are mostly associated with refractive and wave artefacts occurring when the rays pass through the irregular corneal surface and cannot be optically compensated by the device. The use of SHCL as means for making the optic system relatively regular can significantly decrease the artefacts in morphometric measurements. CONCLUSION: The results obtained in this study demonstrate the practicality of tomographic examination in KC with contact correction. The optimal choice is custom-fit SHCL, which along with proper correction of refractive errors also ensures stable position of the lens on the cornea. In standard examination specialists should take into account the «false¼ decrease in parameters of the peripapillary retinal nerve fiber layer and increase in ONH cupping.

8†Unexpected retinopathy in a patient presenting with bilateral optic disc swelling.

A 12-year-old boy presented with 5 day history of blurry vision, 'wobbly eyes', tinnitus and difficulty seeing at night. Local ophthalmology noted bilateral optic disc swelling and referred him urgently for neurological investigations.Clinical Findings: At presentation VA was RE 0.00 and LE 0.2 with normal Ishihara colour vision. His extraocular movements were full without manifest strabismus. Fundoscopy showed bilateral optic disc swelling. Electrophysiology unexpectedly revealed a functionally cone isolated retina with markedly abnormal rod function. Pattern VEPs indicated bilateral macular pathway dysfunction affecting left eye more than right eye. Wide field imaging showed bilateral diffusely scattered yellow-white flecks in the midperiphery of each eye. His kinetic visual fields were moderately restricted bilaterally. MRI showed a Chiari 1 malformation with cerebellar tonsil herniation, but LP opening pressure was normal.Differential diagnosis included RDH5 retinopathy or vitamin A deficiency. On questioning he reported a diet restricted to only meat and biscuits. His vitamin A levels were subnormal at 0.14 umol/L (reference range 0.9-2.5umol/l) and he was started on high-dose Vitamin A supplements.Four months after supplementation retinal appearances had normalised, the rod ERGs recovered, nyctalopia and visual field restriction resolved. PVEPs had improved but an element of LE macular pathway dysfunction remained. Optic disc swelling settled leaving mild temporal pallor, particularly of the LE with some RNFL loss.It is important to recognise nutritional Vitamin A deficiency in children as prompt recognition and treatment can improve symptoms, reverse retinal pathology which we have demonstrated with electrophysiological findings.

Coexistence of open-angle glaucoma and sarcoidosis-associated optic neuropathy.

BACKGROUND: In cases with advanced glaucomatous disc changes, further changes associated with other optic neuropathies cannot be easily identified. We present a case of preexisting open-angle glaucoma and concurrent involvement of sarcoidosis-associated optic neuropathy. CASE PRESENTATION: A 53-year-old man presented with gradual visual loss in his left eye, which began 1 year ago and accelerated 3 months ago. The best-corrected visual acuity in the right eye was 20/20 and counting fingers in the left. Intraocular pressures (IOP) were 12 mmHg in the right eye and 34 mmHg in the left. We diagnosed him with advanced open-angle glaucoma in the left eye based on the advanced glaucomatous cupping of the left optic disc. The IOP in the left eye dropped to 10 mmHg and was well controlled with antiglaucomatous medication; however, his left optic disc developed pallor 3 months after the treatment. The patient was revealed to be diagnosed with sarcoidosis a month ago and had been treated with systemic corticosteroids thereafter by a pulmonologist. Orbital magnetic resonance imaging revealed sarcoidosis-associated optic neuropathy in the left eye. Subsequently, optic neuropathy occurred in his right eye. CONCLUSIONS: In eyes with advanced glaucomatous disc change, detecting the coexistence of other optic neuropathies can be difficult. This report highlights the importance of careful ophthalmic examinations and investigation for etiologies of other optic neuropathies if non-glaucomatous changes are suspected even in eyes with advanced glaucoma.

A unique case of bilateral nanophthalmos and pigmentary retinal abnormality with unilateral angle closure glaucoma and optic disc pit.

BACKGROUND: Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative anterior microphthalmos, and posterior microphthalmos based on the anterior segment: posterior segment ratio. Nanophthalmos can occur in association with optic disc drusen, foveoschisis, and retinitis pigmentosa, as an autosomal recessive syndrome linked to mutations in the MFRP gene. We report a case of bilateral nanophthalmos and pigmentary retinopathy with angle closure glaucoma and optic disc pit in one eye. We believe this to be the first case presenting with optic disc pit in association with nanophthalmos. CASE PRESENTATION: A 56-year-old female presented with bilateral small eyes, high hypermetropia, shallow anterior chamber depth, increased lens thickness, mid-peripheral retinal flecks, and macular edema. She also had high intraocular pressure in the right eye, with a disc cupping of 0.9 with an Optic disc pit. The macular edema in the right eye was found to occur in association with the Optic disc pit, whereas, in the left eye, it was associated with intra-retinal hemorrhages and diagnosed as macular branch retinal vein occlusion secondary to hypertension. She was started on anti-glaucoma medications in both eyes and planned for Anti-VEGF injection in the left eye. CONCLUSION: This case report is unique as it reports an association of Nanophthalmos with Optic Disc pit, with an associated angle closure glaucoma in the same eye, an association which has never been previously reported in the literature.

Impact of 24-Hour Intraocular Pressure on Optic Nerve Fiber Layer Thickness in Patients with Early Diabetic Retinopathy.

Background: The optic nerve fiber layer, composed of ganglion cell axons within the ganglion cell layer, undergoes thickness changes due to diabetic retinopathy. However, the relationship between intraocular pressure (IOP) and optic fiber layer thickness remains unclear. Objective: To investigate the correlation between 24-hour intraocular pressure and optic nerve fiber layer thickness in patients with early diabetic retinopathy. Methods: This retrospective study collected 353 patients with early diabetic retinopathy from January 2019 to December 2021. They were categorized into the retinopathy group (n = 153) and the control group (n = 200). 24-hour IOP and optic fiber layer thickness were assessed, and the correlation between them was analyzed. Results: The observation group exhibited significantly higher 24-hour IOP compared to the control group (16.64 ± 2.58 vs. 15.63 ± 2.52 mmHg, P < .001). Notably, the thickness of upper, lower, nasal, temporal, and average optic nerve fiber layers in the observation group decreased significantly (P < .001). Pearson linear correlation revealed significant negative associations between 24-hour IOP and upper, nasal, temporal, and mean optic nerve fiber layer thickness (R2 = -0.277, -0.399, -0.344, and -0.489, P < .05). The upper, lower, nasal, temporal, and mean optic fiber thickness demonstrated diagnostic value for non-early diabetic retinopathy in type 2 diabetes patients (P < .05), with mean optic fiber thickness displaying the highest diagnostic potential (area under the curve: 0.843, 95% Confidence Interval: 0.803-0.884, P < .001). Conclusions: Thinning of the optic nerve fiber layer in early diabetic retinopathy patients holds predictive value for the condition and exhibits a negative correlation with 24-hour intraocular pressure.

Ocular posterior segment microstructural and microvascular morphological changes in protein supplement-consuming bodybuilders.

BACKGROUND: To determine the effects of protein supplement (whey protein powder (PP)) on retinal, choroidal and optic nerve head (ONH) microstructure and microvascular morphology in healthy bodybuilders. METHODS: This cross-sectional study included 23 male adults (consumers, 23 right eyes) who had been routinely consuming whey PP for bodybuilding purposes for ≥ 3 months, and 21 age- and gender-matched healthy volunteers (non-consumers, 21 right eyes) who also attended the gym but did not consume any nutritional supplements. Participants underwent standard ocular exams, enhanced depth imaging optical coherence tomography (EDI OCT), and optical coherence tomography angiography (OCTA) after ≥ 8 h of rest and fasting. RESULTS: Whey PP was consumed for a median of 9.5 (6-12) months. Whey PP consumers had a median age of 22 (21-22) years, while non-consumers had 21 (20-22) years (p = 0.067). Whey PP consumers had greater microstructural thickness than non-consumers, with subfoveal choroidal thickness (301.40 ± 38.91 versus 278.12 ± 33.58 µm; p = 0.035) being significantly different but not central macular thickness (270.55 ± 24.60 versus 265.85 ± 12.44 µm; p = 0.402). Despite a non-significant difference in superficial and deep capillary plexus vascular densities (VDs), whey PP consumers had relatively lower VDs than non-consumers in all macular regions (p > 0.05). Despite this, whey PP consumers displayed greater ONH VDs, as well as higher global RNFL thickness (116.75 ± 10.41 versus 114.50 ± 11.70 µm) than non-consumers (p > 0.05). CONCLUSION: Protein supplements, particularly whey PPs, appear to be associated with different changes in the retina and choroid, as well as ONH microstructural and microvascular morphology, implying that paying attention to these clinical aspects when performing ocular tests in bodybuilders who consume nutritional supplements could be critical.

Cell-Based Therapies for Glaucoma.

Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways. However, proper integration within the retina and projection to the brain by the newly regenerated neuronal cells remain major hurdles. Meanwhile, a range of methods for in vitro differentiation have been developed to derive retinal cells from a variety of cell sources, including embryonic and induced pluripotent stem cells. More recently, there has been growing interest in the implantation of glial cells as well as cell-derived products, including neurotrophins, microRNA, and extracellular vesicles, to provide functional support to vulnerable structures such as RGC axons and the ONH. These approaches offer the advantage of not relying upon the replacement of degenerated cells and potentially targeting earlier stages of disease pathogenesis. In order to translate these techniques into clinical practice, appropriate cell sourcing, robust differentiation protocols, and accurate implantation methods are crucial to the success of cell-based therapy in glaucoma. Translational Relevance: Cell-based therapies for glaucoma currently under active development include the induction of endogenous regeneration, implantation of exogenously derived retinal cells, and utilization of cell-derived products to provide functional support.

Macular Retinoschisis from Optic Disc without a Visible Optic Pit or Advanced Glaucomatous Cupping (No Optic Pit Retinoschisis [NOPIR]).

PURPOSE: To review eyes with peripapillary and macular retinoschisis without a visible optic pit or advanced glaucomatous optic atrophy, or No Optic Pit Retinoschisis (NOPIR). DESIGN: Retrospective multicenter case series. SUBJECTS: The study included 11 eyes of 11 patients. METHODS: Retrospective study of eyes with macular retinoschisis without a visible optic pit, advanced optic nerve head cupping, or macular leakage on fluorescein angiography. MAIN OUTCOME MEASURES: Visual acuity (VA), retinoschisis resolution, months to resolution, and recurrence of retinoschisis RESULTS: The mean age was 68.1 ± 17.6 years, mean intraocular pressure was 17.4 ± 3.8 mmHg, and the mean spherical equivalent refractive error was -3.1 ± 2.9 diopters. No subject had pathologic myopia. Seven subjects were treated for glaucoma, and 9 subjects had nerve fiber layer defects on OCT. All eyes had retinoschisis in the outer nuclear layer (ONL) in the nasal macula and extending to the edge of the optic disc, and 8 subjects had fovea-involving retinoschisis. Three nonfoveal and 4 fovea-involved eyes were observed, and 4 fovea-involved eyes with vision loss underwent surgery. Surgery involved preoperative juxtapapillary laser followed by vitrectomy and membrane and internal limiting membrane peeling with intraocular gas and face-down position. The mean baseline VA was significantly worse in the surgery group than that in the observation group (P = 0.020). Retinoschisis resolved and vision improved in all surgical cases. The mean resolution time for the surgery group was 2.75 ± 0.96 months, which was shorter than that for the observation group (28.0 ± 21.2 months; P = 0.014). No eye developed recurrence of the retinoschisis after surgery. CONCLUSIONS: Peripapillary and macular retinoschisis can develop in eyes without a visible optic pit or advanced glaucomatous cupping. Eyes without foveal involvement and those with foveal involvement but only mild decrease in vision can be observed for spontaneous resolution. If there is persistent foveal involvement with vision loss, surgery can improve vision by resolving the macular retinoschisis. Surgery for fovea-involved macular retinoschisis without a visible optic pit resulted in faster anatomic resolution and better vision recovery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Longitudinal Assessment of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thicknesses in Patients With Large Optic Disc Cups and Normal Intraocular Pressure and Visual Fields.

PRCIS: The thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) did not change during 5 years in physiological large disc cupping. PURPOSE: We evaluated longitudinal changes in the thicknesses of the cpRNFL and GCC in large disc cupping with a normal intraocular pressure (IOP) (<21 mm Hg) and visual field. METHODS: This retrospective, consecutive case series study included 269 eyes of 269 patients with large disc cupping and normal IOP. We analyzed patient demographics, IOP, central corneal thickness, vertical cup-to-disc ratios using color fundus photography, the thicknesses of the cpRNFL and GCC using RTVue-100, and mean deviation using visual field examinations. RESULTS: The differences in IOP, vertical cup-to-disc ratios, and mean deviation between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the cpRNFL thickness were 106.5±8.5 and 105.1±9.3 µm, respectively; differences between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the GCC thickness were 82.8±9. and 81.5±9.2 µm, respectively; differences between baseline and each follow-up visit were not statistically significant. CONCLUSIONS: The thicknesses of the cpRNFL and GCC did not change in well-maintained optic nerve head findings with normal IOP and visual field during a 5-year follow-up period. Optical coherence tomography evaluations of the thicknesses of the cpRNFL and GCC help accurately diagnose physiological optic disc cupping.

Intravitreal Neuroglobin Mitigates Primate Experimental Glaucomatous Structural Damage in Association with Reduced Optic Nerve Microglial and Complement 3-Astrocyte Activation.

Current management of glaucomatous optic neuropathy is limited to intraocular pressure control. Neuroglobin (Ngb) is an endogenous neuroprotectant expressed in neurons and astrocytes. We recently showed that exogenous intravitreal Ngb reduced inflammatory cytokines and microglial activation in a rodent model of hypoxia. We thus hypothesised that IVT-Ngb may also be neuroprotective in experimental glaucoma (EG) by mitigating optic nerve (ON) astrogliosis and microgliosis as well as structural damage. In this study using a microbead-induced model of EG in six Cynomolgus primates, optical coherence imaging showed that Ngb-treated EG eyes had significantly less thinning of the peripapillary minimum rim width, retinal nerve fibre layer thickness, and ON head cupping than untreated EG eyes. Immunohistochemistry confirmed that ON astrocytes overexpressed Ngb following Ngb treatment. A reduction in complement 3 and cleaved-caspase 3 activated microglia and astrocytes was also noted. Our findings in higher-order primates recapitulate the effects of neuroprotection by Ngb treatment in rodent EG studies and suggest that Ngb may be a potential candidate for glaucoma neuroprotection in humans.

Familial normal tension glaucoma genetics.

Glaucoma is defined by characteristic optic nerve damage and corresponding visual field defects and is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is a strong risk factor for developing glaucoma. However, glaucoma can occur at any IOP. Normal tension glaucoma (NTG) arises with IOPs that are within what has been defined as a normal range, i.e., 21 mm Hg or less, which may present challenges in its diagnosis and management. Identifying inheritance patterns and genetic mutations in families with NTG has helped elucidate mechanisms of NTG, however the pathophysiology is complex and not fully understood. Approximately 2% of NTG cases are caused primarily by mutations in single genes, optineurin (OPTN), TANK binding kinase 1 (TKB1), or myocilin (MYOC). Herein, we review pedigree studies of NTG and autosomal dominant NTG caused by OPTN, TBK1, and MYOC mutations. We review identified mutations and resulting clinical features of OPTN-associated and TBK1-associated NTG, including long-term follow up of these patients with NTG. In addition, we report a new four-generation pedigree of NTG caused by a Glu50Lys OPTN mutation, including six family members with a mean follow up of 17 years. Common features of OPTN -associated NTG due to Glu50Lys mutation included early onset of disease with an IOP <21 mm Hg, marked optic disc cupping, and progressive visual field loss which appeared to stabilize once an IOP of less than 10 mm Hg was achieved. Lastly, we review risk factor genes which have been identified to contribute to the complex inheritance of NTG.