Cerebral Modifications and Visual Pathway Reorganization in Maculopathy: A Systematic Review.

BACKGROUND: Macular degeneration (MD) is one of the most frequent causes of visual deficit, resulting in alterations affecting not only the retina but also the entire visual pathway up to the brain areas. This would seem related not just to signal deprivation but also to a compensatory neuronal reorganization, having significant implications in terms of potential rehabilitation of the patient and therapeutic perspectives. OBJECTIVE: This paper aimed to outline, by analyzing the existing literature, the current understanding of brain structural and functional changes detected with neuroimaging techniques in subjects affected by juvenile and age-related maculopathy. METHODS: Articles using various typologies of central nervous system (CNS) imaging in at least six patients affected by juvenile or age-related maculopathy were considered. A total of 142 were initially screened. Non-pertinent articles and duplicates were rejected. Finally, 19 articles, including 649 patients, were identified. RESULTS: In these sources, both structural and functional modifications were found in MD subjects' CNS. Changes in visual cortex gray matter volume were observed in both age-related MD (AMD) and juvenile MD (JMD); in particular, an involvement of not only its posterior part but also the anterior one suggests further causes besides an input-deprivation mechanism only. White matter degeneration was also found, more severe in JMD than in AMD. Moreover, functional analysis revealed differences in cortical activation patterns between MD and controls, suggesting neuronal circuit reorganization. Interestingly, attention and oculomotor training allowed better visual performances and correlated to a stronger cortical activation, even of the area normally receiving inputs from lesioned macula. CONCLUSION: In MD, structural and functional changes in cerebral circuits and visual pathway can happen, involving both cerebral volume and activation patterns. These modifications, possibly due to neuronal plasticity (already observed and described for several brain areas), can allow patients to compensate for macular damage and gives therapeutic perspectives which could be achievable through an association between oculomotor training and biochemical stimulation of neuronal plasticity.

Diagnostic ability of OCT parameters and retinal ganglion cells count in identification of glaucoma in myopic preperimetric eyes.

BACKGROUND: The aim of the study is to evaluate the diagnostic ability of OCT parameters and retinal ganglion cells (RGCs) count in identify glaucomatous disease in myopic preperimetric eyes. METHODS: This was a cross-sectional observational study. The study group consisted of 154 eyes: 36 controls, 64 preperimetric (PPG), and 54 primary openangle glaucoma (POAG) eyes. Each group was divided into three subgroups based on axial length: emmetropic, myopic with axial length (AL) < 25 mm, and myopic with AL > 25 mm, to analyze the effect of myopia. The RGCs count was obtained using a model described later. As regard the influence of myopia on OCT parameters and RGC count, we performed Pearson's correlation. The Area Under Receiver Operator Characteristics Curves (AUROC curves) evaluated which parameter had the best sensitivity and specificity in identifying glaucoma in myopic eyes. RESULTS: In Pearson's test, all Ganglion Cell Complex (GCC) thicknesses showed the weakest and less significant correlation with AL in all groups. All the AUROCs were statistically significant, and above 0.5. Inferior GCC and Global Loss Volume (GLV) showed the highest AUCs in all myopic group and the best diagnostic ability in distinguishing control from glaucomatous eyes. RGCcount showed good AUROC in all groups, with sensitivities of about 83% in myopic eyes, and specificity over 91% in all groups. CONCLUSIONS: GCC is the parameter less influenced by the AL, and the inferior GCC and the GLV have the best diagnostic performance. The RGCcount has good sensitivity and specificity, so it can be used as a complementary test in the diagnosis of glaucoma in myopic preperimetric eyes.

Assessing the Performance of Daily Intake of a Homotaurine, Carnosine, Forskolin, Vitamin B2, Vitamin B6, and Magnesium Based Food Supplement for the Maintenance of Visual Function in Patients with Primary Open Angle Glaucoma.

BACKGROUND: Glaucoma is a multifactorial optic neuropathy, which causes a continuous loss of retinal ganglion cells. Given the neurodegenerative nature of glaucoma, the necessity for neuroprotective intervention still arises, to be added alongside hypotonic therapy. OBJECTIVE: The objective of this study was to assess the effect of daily intake of a homotaurine, carnosine, forskolin, vitamins B1, B2, and B6, folic acid, and magnesium based supplement (GANGLIOLIFE®) on the progression rates of the visual field in patients with progressive POAG despite good tonometric compensation and to assess the most suitable dosage. METHODS: This is a monocentric nonrandomized experimental clinical study. Patients with mean deviation (MD) ranging from -2 dB to -15 dB with MD progression ≥1 dB in the previous year and IOP values of ≤18 mm Hg were included. All the patients underwent supplement therapy for a period of 6 months. For the first 2 months, they took 2 tablets a day, and for the following 4 months, 1 tablet a day. The patients were assessed before the start of treatment, time 0 (T 0), after 2 months (T 1), and after 6 months (T 2) of therapy. At each check-up, patients were given a full eye test including perimetry, RNFL, and GCC using FD-OCT, PERG, contrast sensitivity, and QoL evaluation using the Glaucoma Symptom Scale questionnaire and National Eye Institute Visual Function Questionnaire 25. RESULTS: 31 patients with a mean age of 70.80 ± 8.77 were included. At T 1 and T 2, the mean values of MD were lessened (MD = -5.37 ± -2.91, P < 0.01, and MD = -5.48 ± 3.15, P < 0.05, respectively) compared to T 0 (MD = -5.98 ± 2.83). Patients also demonstrated a significant reduction in IOP (P < 0.01), improved light sensitivity (P < 0.01) and contrast sensitivity (P < 0.05), and a better quality of life (P < 0.05). CONCLUSIONS: Treatment with a supplement which includes homotaurine, carnosine, forskolin, vitamins B1, B2, and B6, folic acid, and magnesium has been shown to be able to slow down the rate of progression of functional damage and improve visual function after 2 and 6 months of daily intake. Quality of life showed significant improvement.

Retinal microvasculature in pituitary adenoma patients: is optical coherence tomography angiography useful?

PURPOSE: To examine retinal vascular changes in the peripapillary and macular areas in patients with pituitary adenoma (PA) using optical coherence tomography angiography (OCTA). METHODS: Cross-sectional, retrospective study of 17 consecutive PA patients and 16 healthy subjects. All patients underwent a neuro-ophthalmological examination to assess the presence of optic neuropathy (ON). Static automated perimetry (SAP), macular and optic disc structural OCT [retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thicknesses] and OCTA were performed. Pituitary adenoma (PA) patients with ON were compared to those without ON and to healthy subjects. RESULTS: Optic neuropathy (ON) was found in 16 eyes of nine PA patients. Peripapillary vessel density (ppVD) and macular vessel density (VD) in the superficial vascular plexus were significantly decreased in PA eyes with ON, compared to healthy eyes (45.21 ± 5.69 versus 50.52 ± 2.14% and 43.79 ± 5.03% versus 48.96 ± 2.94%, respectively). No significant difference in VD was observed in the macular deep vascular complex (DVC) between groups. Pituitary adenoma (PA) patients with ON had a mean ppVD reduction by 10.51% compared to healthy subjects. RNFL and GCC thicknesses were significantly reduced in PA eyes with ON compared to the other groups. Peripapillary VD (ppVD) significantly correlated with RNFL thickness and SAP mean deviation. CONCLUSIONS: Optical coherence tomography angiography showed a significant decrease in ppVD and superficial macular VD in PA eyes with ON compared to healthy eyes, according to RNFL and GCC thinning. Together with the absence of DVC alterations, it may provide further insights into neurovascular coupling.

Diagnostic Ability and Discriminant Values of OCT-Angiography Parameters in Early Glaucoma Diagnosis.

PURPOSE: To evaluate papillary, peripapillary, and macular vasculature with optical coherence tomography angiography in preperimetric (PPG), primary open-angle glaucoma (POAG), and normal eyes, and to assess diagnostic ability and associations among the vasculature and structural damage. METHODS: This was an observational, cross-sectional study. Retinal nerve fiber layer (RNFL), ganglion cell complex thickness, whole-image (wiVD), inside disc (idVD), peripapillary (ppVD), and macular vessel densities were obtained. Analysis of variance, post hoc test, and Pearson coefficient were used. The areas under the receiver operating characteristic curve (AUC) and cut-offs were calculated. RESULTS: Thirteen healthy, 39 PPG, and 19 POAG eyes were included. Papillary and peripapillary VD were lower in POAG eyes in all parameters analyzed. wiVD in PPG eyes (52.37 ± 5.04%) was significantly decreased compared to healthy eyes (58.02 ± 2.02%, p < 0.05). AUC ranged from 0.62 to 0.90; the established cut-off values were 56% for wiVD, 55% for idVD, and 62% for ppVD. Pearson's correlation coefficient showed a direct correlation between the papillary or peripapillary VD and RNFL thickness. CONCLUSIONS: Vessel densities in POAG eyes are significantly lower than in healthy eyes, and they show good discriminatory abilities. A diminished microvascular network is associated with RNFL thinning more strongly in POAG than in PPG eyes.

Reading Ability in Primary Open-angle Glaucoma: Evaluation with Radner Reading Charts.

SIGNIFICANCE: This study determined the impact of visual disabilities caused by glaucoma on the patient's everyday life and emphasized the importance of developing strategies to improve reading ability in primary open-angle glaucoma (POAG) patients. PURPOSE: The purposes of this study were to investigate the reading performances of patients affected by POAG using the Italian version of the Radner Reading Charts and to test the presence of correlation between visual field (VF) damage and reading parameters. METHODS: In this cross-sectional observational study, all patients underwent a complete ophthalmic evaluation including VF testing and evaluation of reading performance using the Radner Reading Charts. The parameters for testing reading performance were reading acuity in logRAD, reading speed in words per minute, maximum reading speed, critical print size, and reading mistakes. Primary open-angle glaucoma and healthy groups were compared using the Mann-Whitney U test. The correlation between VF and reading parameters in glaucomatous eyes was assessed using Spearman correlation analysis. Based on VF mean deviation, each POAG patient had differences in reading performance between his/her best and worst eyes when compared using the paired Wilcoxon test. Statistical significance was set at P ≤ .05. RESULTS: Eighty POAG patients and 60 healthy controls were enrolled. Glaucomatous subjects read slowly (166.63 ± 29.40 vs. 193.84 ± 26.20 words per minute, P < .0001) and made more mistakes than did healthy subjects. The critical print size for POAG patients was larger than the one for controls (0.52 ± 0.18 vs. 0.62 ± 0.16, P < .0001). Reading parameters showed a moderate correlation with VF mean deviation. The reading parameters were significantly impaired in the worst eye, and this result confirms the impact of VF loss on reading ability. CONCLUSIONS: This study demonstrated that glaucomatous patients read slowly and with more errors. Reading performances showed a good correlation with VF defect.

Changes of Visual Pathway and Brain Connectivity in Glaucoma: A Systematic Review.

Background: Glaucoma is a leading cause of irreversible blindness worldwide. The increasing interest in the involvement of the cortical visual pathway in glaucomatous patients is due to the implications in recent therapies, such as neuroprotection and neuroregeneration. Objective: In this review, we outline the current understanding of brain structural, functional, and metabolic changes detected with the modern techniques of neuroimaging in glaucomatous subjects. Methods: We screened MEDLINE, EMBASE, CINAHL, CENTRAL, LILACS, Trip Database, and NICE for original contributions published until 31 October 2017. Studies with at least six patients affected by any type of glaucoma were considered. We included studies using the following neuroimaging techniques: functional Magnetic Resonance Imaging (fMRI), resting-state fMRI (rs-fMRI), magnetic resonance spectroscopy (MRS), voxel- based Morphometry (VBM), surface-based Morphometry (SBM), diffusion tensor MRI (DTI). Results: Over a total of 1,901 studies, 56 case series with a total of 2,381 patients were included. Evidence of neurodegenerative process in glaucomatous patients was found both within and beyond the visual system. Structural alterations in visual cortex (mainly reduced cortex thickness and volume) have been demonstrated with SBM and VBM; these changes were not limited to primary visual cortex but also involved association visual areas. Other brain regions, associated with visual function, demonstrated a certain grade of increased or decreased gray matter volume. Functional and metabolic abnormalities resulted within primary visual cortex in all studies with fMRI and MRS. Studies with rs-fMRI found disrupted connectivity between the primary and higher visual cortex and between visual cortex and associative visual areas in the task-free state of glaucomatous patients. Conclusions: This review contributes to the better understanding of brain abnormalities in glaucoma. It may stimulate further speculation about brain plasticity at a later age and therapeutic strategies, such as the prevention of cortical degeneration in patients with glaucoma. Structural, functional, and metabolic neuroimaging methods provided evidence of changes throughout the visual pathway in glaucomatous patients. Other brain areas, not directly involved in the processing of visual information, also showed alterations.

Long-term outcomes after acute primary angle closure of Caucasian chronic angle closure glaucoma patients.

IMPORTANCE: There is a lack of information about long-term results of chronic angle closure glaucoma following an acute primary angle closure attack in Caucasian patients. PURPOSE: The aim of the study was to report morphological and functional long-term data of chronic angle closure eyes following a monolateral primary angle closure attack and to provide a comparison with their fellow eyes. DESIGN: Observational retrospective case series. PARTICIPANTS: Fifty-seven consecutive patients (114 eyes) underwent long-term follow-up analysis. METHODS: Patients underwent ophthalmic assessment more than 5 years since the angle closure attack. MAIN OUTCOME MEASURES: Intraocular pressure, best-corrected visual acuity, angle assessment, vertical C/D ratio and standard automated perimetry were the main outcome measures. Comparisons were made between angle closure attack eyes and fellow eyes and between phakic and pseudophakic eyes. RESULTS: Mean follow-up time was 5.86 ± 1.19 years. A significant greater damage in the angle closure eyes compared with fellow eyes in both structural (mean C/D 0.61 ± 0.16; P < 0.001) and functional (mean deviation: -7.98 ± 6.46 vs. -4.83 ± 4.95 dB; P < 0.001) terms was present. Mean IOP was 13.44 ± 2.78 and 13.89 ± 2.60 mmHg in angle closure and fellow eyes (P = 0.11). Thirty of 57 (53%) fellow eyes developed chronic angle closure (mean deviation: -7.74 ± 5.21 dB) even if prophylactic iridotomy was promptly performed. CONCLUSION AND RELEVANCE: Our study prompts ophthalmologists to closely follow patients after an APAC attack to prevent potential glaucoma damage in both APAC and fellow eye.

Targeted next generation sequencing in Italian patients with Usher syndrome: phenotype-genotype correlations.

We report results of DNA analysis with next generation sequencing (NGS) of 21 consecutive Italian patients from 17 unrelated families with clinical diagnosis of Usher syndrome (4 USH1 and 17 USH2) searching for mutations in 11 genes: MYO7A, CDH23, PCDH15, USH1C, USH1G, USH2A, ADGVR1, DFNB31, CLRN1, PDZD7, HARS. Likely causative mutations were found in all patients: 25 pathogenic variants, 18 previously reported and 7 novel, were identified in three genes (USH2A, MYO7A, ADGRV1). All USH1 presented biallelic MYO7A mutations, one USH2 exhibited ADGRV1 mutations, whereas 16 USH2 displayed USH2A mutations. USH1 patients experienced hearing problems very early in life, followed by visual impairment at 1, 4 and 6 years. Visual symptoms were noticed at age 20 in a patient with homozygous novel MYO7A missense mutation c.849G > A. USH2 patients' auditory symptoms, instead, arose between 11 months and 14 years, while visual impairment occurred later on. A homozygous c.5933_5940del;5950_5960dup in USH2A was detected in one patient with early deafness. One patient with homozygous deletion from exon 23 to 32 in USH2A suffered early visual symptoms. Therefore, the type of mutation in USH2A and MYO7A genes seems to affect the age at which both auditory and visual impairment occur in patients with USH.

Minimally-invasive glaucoma surgeries (MIGS) for open angle glaucoma: A systematic review and meta-analysis.

BACKGROUND: MIGS have been developed as a surgical alternative for glaucomatous patients. PURPOSE: To analyze the change in intraocular pressure (IOP) and glaucoma medications using different MIGS devices (Trabectome, iStent, Excimer Laser Trabeculotomy (ELT), iStent Supra, CyPass, XEN, Hydrus, Fugo Blade, Ab interno canaloplasty, Goniscopy-assisted transluminal trabeculotomy) as a solo procedure or in association with phacoemulsification. METHODS: Randomized control trials (RCT) and non-RCT (non randomized comparative studies, NRS, and before-after studies) were included. Studies with at least one year of follow-up in patients affected by primary open angle glaucoma, pseudoexfoliative glaucoma or pigmentary glaucoma were considered. Risk of Bias assessment was performed using the Cochrane Risk of Bias and the ROBINS-I tools. The main outcome was the effect of MIGS devices compared to medical therapy, cataract surgery, other glaucoma surgeries and other MIGS on both IOP and use of glaucoma medications 12 months after surgery. Outcomes measures were the mean difference in the change of IOP and glaucoma medication compared to baseline at one and two years and all ocular adverse events. The current meta-analysis is registered on PROSPERO (reference n° CRD42016037280). RESULTS: Over a total of 3,069 studies, nine RCT and 21 case series with a total of 2.928 eyes were included. Main concerns about risk of bias in RCTs were lack of blinding, allocation concealment and attrition bias while in non-RCTs they were represented by patients' selection, masking of participants and co-intervention management. Limited evidence was found based on both RCTs and non RCTs that compared MIGS surgery with medical therapy or other MIGS. In before-after series, MIGS surgery seemed effective in lowering both IOP and glaucoma drug use. MIGS showed a good safety profile: IOP spikes were the most frequent complications and no cases of infection or BCVA loss due to glaucoma were reported. CONCLUSIONS: Although MIGS seem efficient in the reduction of the IOP and glaucoma medication and show good safety profile, this evidence is mainly derived from non-comparative studies and further, good quality RCTs are warranted.

Retinal and Macular Ganglion Cell Count Estimated With Optical Coherence Tomography RTVUE-100 as a Candidate Biomarker for Glaucoma.

PURPOSE: To evaluate the ability of total and macular estimated retinal ganglion cell (RGC) counts to discriminate between healthy and glaucomatous eyes. To determine threshold markers of the estimated RGCs taking into account age dependence. METHODS: This was a cross-sectional, observational study. The study group consisted of 176 eyes subdivided in three groups: 32 healthy, 91 preperimetric (PPG), and 53 primary open-angle glaucoma (POAG) eyes. The estimate of total and macular number of RGCs was obtained using a model described later. To account for the inverse correlation of RGC count with age, we considered two age subgroups (≤55 and >55 years) for both total and macular estimated RGC counts. We computed frequency distributions and receiver operating characteristic (ROC) curves to measure the discriminating ability and derive the cut-offs between two different conditions with their relative diagnostic parameters. RESULTS: The total and macular estimated RGC counts showed highly significant differences among the three groups (P < 0.0001). The estimated RGC counts performed fairly well in distinguishing healthy from glaucomatous (PPG+POAG) eyes (area under the curve [AUC] = 0.79-0.92) with no statistically significant difference between total and macular RGCs. The approach allowed a good discrimination also between PPG and POAG eyes (AUC = 0.86-0.92). Cutoffs for the older age bracket were found to be lower in all cases. CONCLUSIONS: Retinal ganglion cell counts estimated with empirical formulas with RTVue-100 could be used as a valid surrogate for neural losses in glaucoma.

Long-term efficacy of deep sclerectomy in Posner-Schlossman syndrome.

The Posner-Schlossman syndrome (PSS) is an elusive disease that can lead to serious consequences such as glaucomatous damage. Deep sclerectomy has been proven thus far to be the most effective surgical intervention to keep intraocular pressure (IOP) elevation under control compared with other surgical techniques, because it presents the least amount of postoperative complications. The aim of this case report is to demonstrate the efficacy of deep sclerectomy with T-Flux and the long-lasting effects that persist after 7 years in an eye affected by PSS. This case report demonstrates that an intervention of deep sclerectomy can lead to excellent results in terms of visual acuity as well as IOP lowering early in the history of the patient affected by PSS so that it can preclude establishment of glaucomatous damage.

Retinal nerve fibre layer and macular thickness analysis with Fourier domain optical coherence tomography in subjects with a positive family history for primary open angle glaucoma.

AIM: To detect early structural changes of retinal nerve fibre layer (RNFL) and macular ganglion cell complex (GCC) in subjects with a positive family history for primary open angle glaucoma (POAG) using Fourier domain optical coherence tomography (FD-OCT) (RTVue-100). METHODS: This was a cross-sectional observational study. First and second degree relatives of POAG patients, healthy subjects, and subjects with preperimetric glaucoma (PPG) without a family history for glaucoma, were enrolled. All participants underwent complete ophthalmic examination, visual field test and FD-OCT (RTVue-100) imaging. Average RNFL and GCC thicknesses were measured and a pattern analysis was applied to the GCC map. Analysis of variance (ANOVA), least significant difference post-hoc test, and multiple ANOVA were used. RESULTS: The final analysis included 271 eyes divided into several groups: 163 eyes of first and second degree relatives (85 healthy, 40 with ocular hypertension and 38 with PPG); and 108 eyes of subjects without a positive family history (60 healthy and 48 PPG). RNFL and GCC thickness values of these five groups were statistically different (p<0.001). RNFL superior, GCC average, GCC superior, and GCC inferior were found to be significantly thinner and the global loss volume was higher in normal relatives than in healthy subjects without a positive family history of POAG (p=0.04, p=0.001, p=0.005, p=0.004, p=0.009). RNFL and GCC thicknesses obtained by dividing the family members by the degree of consanguinity showed statistically significant thinning in siblings of glaucomatous subjects than in offspring. CONCLUSIONS: Our study shows that the eyes of subjects with a positive family history for POAG have significantly thinner RNFL and GCC than normal eyes and a more accurate follow-up has to be performed.