Molecular Biologic Milieu in Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy: A Literature Review.

Multiple lines of evidence support an immunologic response along with inflammation to be implicated in the pathophysiology of primary rhegmatogenous retinal detachment (RRD) and the development of proliferative vitreoretinopathy (PVR). The purpose of this review is to provide an update on the signaling molecules in the vitreous and subretinal fluid (SRF) involved in these processes. A detailed literature search was performed in PubMed database until November 2021. We identified all papers referring to inflammatory and immunological mediators in the context of primary RRD and in cases complicated by PVR. We analyzed prospective and retrospective cohort studies and reference lists of the retrieved articles. A comprehensive investigation of immunological and inflammatory responses provides significant evidence for the implication of varying signaling molecules in the pathophysiology of RRD and the development of PVR. The reviewed series has revealed that disruption of the normal equilibrium during these processes may be present in the vitreous and SRF of these eyes. The precise role of cytokines, chemokines, and growth factors in the pathophysiology of these disorders remains to be clearly elucidated. Overall, immunological and inflammatory signaling molecules are widely implicated in both primary RRD and PVR. The reviewed literature indicates that precise knowledge concerning the pathological milieu sheds light on the underlying pathophysiology and potential therapeutic targets and highlights unmet needs to be addressed by future research.

Strabismus surgery for diplopia in chronic progressive external ophthalmoplegia.

BACKGROUND: To report midterm outcomes of strabismus strategy for management of diplopia in chronic progressive external ophthalmoplegia and specific surgical planning rationale. DESIGN: Retrospective interventional case series. RESULTS: Two patients, a 26-year-old male and a 36-year-old female, diagnosed with chronic progressive external ophthalmoplegia presented with blepharoptosis and intermittent diplopia. Ocular motility examination was significant for bilateral profound impairment of adduction with relative preservation of abduction, infraduction and elevation. Control of intermittent exotropia gradually worsened over 3 and 1.5 years of follow-up, respectively, in the presence of documented stability of the angle of exodeviation. Strabismus surgery involving modest amounts of bilateral medial rectus resection and lateral rectus recessions was undertaken. Surgical intervention was successful in controlling alignment in primary position and alleviating diplopia and asthenopia after 9 and 8 years of follow-up time, respectively, despite slow progression of ophthalmoplegia. CONCLUSION: Bilateral selective impairment of adduction and intermittent exotropia may be the presenting ocular motility disturbance in chronic progressive external ophthalmoplegia. Properly designed strabismus surgery may provide sustainable, in the midterm, control of alignment and symptomatic relief in selected patients with CPEO.

Tectonic epikeratoplasty with ethanol-stored donor corneas.

To evaluate the efficacy and outcomes of tectonic epikeratoplasty with use of ethanol-preserved corneal grafts for the management of perforated corneal melts. The present retrospective case series includes 10 eyes which underwent tectonic epikeratoplasty for perforated corneal melts. The stromal remainders of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) graft preparation were stored in 95% ethanol and used as emergency tectonic grafts for restoring globe integrity after sterile and infectious perforated corneal melts. In 6 cases with subtotal corneal melt, DMEK remainders (endothelium-denuded corneoscleral buttons) were used for 'limbus to limbus' tectonic epikeratoplasty and in 4 cases DSAEK remainders (anterior stroma) were used to seal focal perforated melts. Graft storage time was 5.1 ± 4.9 (ranging from 0.5 to 17) months. The surgeries were successful in all cases with restitution of the globe integrity. During the postoperative course 4 cases developed a graft melt (corneoscleral button for limbus to limbus tectonic epikeratoplasty, n = 3; lamellar patch, n = 1) within 2-6 months after the initial procedure. Three patients underwent successful repeat tectonic epikeratoplasty. In the fourth case of graft melt the globe was enucleated due to underlying expulsive haemorrhage and severe pain. The short-term results of the present case series suggest that the use of ethanol-stored stromal remainder of donor corneas after endothelial keratoplasty is an efficient temporary measure for tectonic restoration of perforated corneas.

"Double scleral tunnel in tandem" technique for glaucoma drainage tube implants.

PURPOSE: To describe a new technique of Ahmed glaucoma valve implantation in patients with refractory glaucoma and present the long-term results. METHODS: Twenty-eight eyes of 28 patients with refractory glaucoma participated in the study. "Double scleral tunnel in tandem" technique was used for glaucoma valve implantation in all patients. The technique consists of the formation of two scleral tunnels in tandem so as to completely cover the extraocular part of valve's tube and facilitate a parallel to the iris placement of the intraocular part of the tube. RESULTS: Postoperative hypotony developed in two (7.1%) cases which resolved within 3 days in all cases. One (3.6%) eye manifested postoperative hyphema that resolved without complications within a week, and two (7.1%) cases presented with exposure of the tube. The average highest postoperative intraocular pressure (IOP) during the follow-up period was 19 mmHg (range 8-38 mmHg) without medications, and the average IOP at the last follow-up visit was 14.5 mmHg (range 8-22 mmHg). Additional treatment for IOP control was necessary in 11 (39.3%) cases. The average follow-up period was 60 months. CONCLUSION: This novel technique was found to be easy to master, effective and with low cost and rate of complications.

Supradescemetic voriconazole injection for Candida parapsilosis keratitis.

PURPOSE: To describe a technique for intracorneal application of voriconazole into the supradescemetic space in a case of deep recalcitrant Candida parapsilosis keratitis of a penetrating cornea graft. METHODS: A deep intracorneal incision reaching the center of the corneal infiltrate was created with a 20-gauge MVR blade. Then, a 27-gauge hydrodissection cannula was inserted deep into the corneal pocket, and 0.1 ml of voriconazole 0.5 mg/ml was injected until a bullous detachment of Descemet membrane (DM) covered 1/3 of the graft's area. DM detachment was documented by anterior segment optical coherence tomography (AS-OCT). RESULTS: AS-OCT confirmed the creation of a drug depot in the supradescemetic space, which partially regressed during the following hours; 24 h after the injection, a complete reattachment of DM was documented. After 4 weeks, the stromal infiltrate has cleared completely and no signs of recurrence were observed 3 months after injection. CONCLUSION: In the present case, the supradescemetic voriconazole injection led to resolution of a deep recalcitrant fungal infiltrate. The herein described technique could be tried in similar cases, where an intrastromal injection is indicated, as it may offer a larger intracorneal drug depot.

Electrophysiological assessment for early detection of retinal dysfunction in ß-thalassemia major patients.

PURPOSE: The purpose of this study was to assess the role of various diagnostic tests in early detection of retinal changes in ß-thalassemia major patients. METHODS: Thirty-eight visually asymptomatic ß-thalassemia major patients receiving regular blood transfusions and iron-chelation therapy with deferoxamine (group A, n = 13), deferasirox (group B, n = 11) or deferoxamine with deferiprone (group C, n = 14) and fourteen age- and sex- matched healthy individuals were included in the study. All participants underwent ophthalmoscopy, full-field electroretinography (ERG), visual evoked potentials (VEP), multifocal electroretinography (mfERG), fundus autofluorescence (FAF) imaging and optical coherence tomography (OCT) scans. RESULTS: Retinal pigment epithelium changes were present in two cases. Scotopic ERG demonstrated decreased a-wave amplitude in groups A, B and C (p = 0.03, p = 0.002 and p = 0.002, respectively) and decreased b-wave amplitude in groups B and C (p = 0.002 and p = 0.01, respectively) compared to controls. Photopic ERG showed delayed b-wave latency in groups A and C (p = 0.03 and p = 0.03, respectively) ERG maximal combined response and VEP response did not differ between groups. MfERG showed reduced retinal response density in ring 1 in groups A, B, C (p < 0.001, p < 0.001, p = 0.001, respectively) and ring 2 in group B (p = 0.02) and delayed latency in ring 5 in groups A and B (p = 0.04 and p = 0.04, respectively). Abnormal FAF images appeared in three cases and OCT abnormalities in one case, whereas no changes were observed in controls (p = 0.55 and p = 1.00, respectively). CONCLUSIONS: Full-field ERG and mfERG are more sensitive tools for detecting early retinal changes in ß-thalassemia patients compared with ophthalmoscopy, VEP, FAF imaging and OCT scans.

BAX and BCL2 Gene Polymorphisms in Rhegmatogenous Retinal Detachment.

PURPOSE: The purpose of this study was to investigate the potential association between rhegmatogenous retinal detachment (RRD) and BAX and BCL2 polymorphisms. METHODS: This is a case control study of 99 patients with RRD and 120 healthy control subjects of Greek origin, surveyed for BAX and BCL2 polymorphisms (rs2279115 and rs4645878) and a potential correlation to RRD. RESULTS: The rs4645878 AA genotype was found to be significantly associated with RRD (p = 0.003; OR: 6.89, 95% CI: 1.76-26.93), while the rs2279115 CC genotype as well as the C allele was not found in patients with RRD. CONCLUSIONS: This is the first study evaluating the potential relationship between BCL2 and BAX gene polymorphisms and RRD in a Greek population, showing a significant association between BAX rs4645878 polymorphism and RRD susceptibility. This finding suggests that an apoptotic mechanism is implicated in the pathogenesis of RRD.

Postoperative eccentric macular holes after vitrectomy and internal limiting membrane peeling.

The purpose of this study was to describe the incidence, clinical characteristics, and outcome of eccentric macular holes presenting after vitrectomy and internal limiting membrane (ILM) peeling for the treatment of macular pathology and discuss the pathogenesis of holes formation. A retrospective, noncomparative, interventional case-series study of five patients who developed eccentric macular holes postoperatively following vitrectomy in 198 consecutive patients who underwent ILM peeling for idiopathic macular hole and epiretinal membrane formation between 2008 and 2015. Five patients (2.5 %) developed full-thickness eccentric macular holes postoperatively. Three patients presented with a single eccentric macular hole, one patient had an eccentric hole after a failed idiopathic macular hole surgery and one patient developed four eccentric macular holes. The mean diameter of the holes was 584 µm (range 206-1317 µm) and the average time of holes formation after vitrectomy was 27.7 weeks (range 1-140 weeks). Postoperative best-corrected visual acuity ranged from "counting fingers" to 20/25. The eyes with the holes distant from the fovea had the best final visual acuity. No further intervention was attempted and no complications occurred. The mean follow-up time was 26.8 months. The postoperative macular holes after vitrectomy and ILM peeling were variable in number, size, and time of appearance but remained stable and were not associated with any complications. The pathogenesis of macular holes is most consistent with contraction of the residual ILM or secondary epimacular proliferation probably stimulated by ILM peeling.

PREVALENCE OF THE COMPLEMENT FACTOR H AND GSTM1 GENES POLYMORPHISMS IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: The purpose of our study was to investigate the potential association between the complement factor H (CFH) (rs3753394, rs800292, rs2284664, rs1329428, and rs1065489) and GSTM1 gene polymorphisms, and central serous chorioretinopathy (CSCR) susceptibility in a well-defined Greek cohort. METHODS: We enrolled a case-control study in a Greek population with 41 cases and 78 controls. Five milliliters of peripheral blood was collected from each participant, and DNA was extracted using the PureLink Genomic DNA kit. The CFH (rs3753394, rs800292, rs2284664, rs1329428, and rs1065489) single nucleotide polymorphisms and GSTM1 polymorphism were tested using polymerase chain reaction assays. RESULTS: Between CSCR (n = 41) cases and controls (n = 78), the TT rs3753394, GG rs1329428, and TT rs1065489 genotypes' frequencies of the CFH gene were found to be significantly associated with risk of CSCR. The genotype frequency of the CFH rs2284664, rs800292, and of the GSTM1 gene polymorphisms was not found to be significantly associated with CSCR. CONCLUSION: Our results demonstrated a significant association between CSCR and single nucleotide polymorphisms in the CFH gene (rs3753394, rs1329428, and rs1065489), suggesting that disturbances in choroidal vasculature, through intercorrelation with adrenomedullin, play a significant role in CSCR pathogenesis.

Scleral Buckling versus Vitrectomy for Retinal Detachment Repair: Comparison of Visual Fields and Nerve Fiber Layer Thickness.

PURPOSE: To compare visual field loss and retinal nerve fiber layer (RNFL) defects in cases of rhegmatogenous retinal detachment (RRD) treated with scleral buckle (SB) versus pars plana vitrectomy (PPV) and C3F8 injection. METHODS: This was a prospective, comparative interventional study of 50 eyes with primary RRD, treated with PPV (25 eyes) or SB (25 eyes). All measurements took place at least 9 months following successful and uncomplicated surgical treatment. The visual field total deviation (TD) values for preoperative attached and detached areas were calculated and compared separately. The optic nerve head morphology was studied with Heidelberg retinal tomography (HRT), and the RNFL using spectral-domain optical coherence tomography. RESULTS: The preoperative detached areas demonstrated more affected TD values (in dB) compared to the preoperative attached areas (-6.9 ± 5.2 vs. -4.3 ± 3.3 for the SB group and -9.6 ± 5.2 vs. -7.8 ± 5.1 for the PPV group; p = 0.001) in both groups. The preoperative attached areas of the SB group showed better TD values (calculated mean values) compared to the preoperative attached areas of the PPV group (-4.3 ± 3.3 vs. -7.8 ± 5.1, p = 0.007). The RNFL and HRT values showed no statistically significant difference between the two groups. CONCLUSIONS: It seems that the preoperative detached retina, despite successful reattachment, suffers permanent damage as a result of the detachment, irrespective of the method of treatment. In the PPV group, the postoperative functionality of the preoperative attached areas was detected to be worse compared to the postoperative functionality of the preoperative attached areas of the SB group. We postulate that this fact could be attributed to an additional traumatizing factor (possibly fluid-air exchange or gas injection) in patients with RRD treated with PPV.

Clinical, anatomical, and electrophysiological assessments of the central retina following intravitreal bevacizumab for macular edema secondary to retinal vein occlusion.

The purpose of this study is to evaluate the long-term visual, anatomical and electrophysiological outcomes of repeated intravitreal injections of bevacizumab for macular edema due to retinal vein occlusion (RVO) and investigate any possible toxic effects on the central fovea. This is a prospective, noncomparative, interventional case series. Thirty-three eyes of 33 patients with macular edema secondary to RVO were treated with 1.25 mg/0.05 ml intravitreal bevacizumab. Nine patients had nonischemic central retinal vein occlusion (CRVO) and 24 patients had branch retinal vein occlusion (BRVO). The main outcome measures were best-corrected visual acuity, central retinal thickness (CRT), and multifocal electroretinography (mfERG) responses changes at baseline, 1 month after the third injection and at the end of the 2-year long follow-up period. Patients with CRVO had mean best-corrected Snellen visual acuity of 0.10 at baseline, which improved significantly to 0.31 after 2 years (P = 0. 028).The mean CRT at presentation was 756.28 µm and reduced significantly to 439.14 µm after 2 years (P = 0.05). Patients with BRVO had mean best-corrected Snellen visual acuity of 0.19 at baseline, which improved significantly to 0.40 after 2 years (P < 0.001). The mean CRT at presentation was 681.04 µm and reduced significantly to 369.81 µm after 2 years (P < 0.001). Mean mfERG responses within central 10° (ring1, ring2) showed statistically significant differences on P1 parameters in terms of response density and implicit time after 2 years in both CRVO and BRVO patients. Repeated intravitreal bevacizumab injections for macular edema due to either CRVO or BRVO resulted in long-term improvement of visual acuity, a reduction in CRT and statistically significant changes in the mfERG responses with nondemonstrable toxic effects on the central fovea.

Intravitreal cilium associated with retinal detachment 40 years following penetrating eye injury: a case report.

BACKGROUND: The presence of an intraocular cilium is very rare and the response of the eye to the cilium is variable. We present the case of a patient with a cilium found in the vitreous cavity during vitrectomy for rhegmatogenous retinal detachment 40 years following penetrating eye injury. To our knowledge, this is the longest reported presence of a cilium in the vitreous cavity. CASE PRESENTATION: A 70-year-old Caucasian woman presented to the emergency department of our hospital complaining of sudden visual impairment and floaters of her right eye initiated 2 weeks earlier. Ophthalmic history included a penetrating injury of the right eye with a sharp metallic object 40 years ago and an uncomplicated phacoemulsification surgery in the same eye 2 years earlier. Fundoscopy revealed an inferior macula off rhegmatogenous retinal detachment. No inflammation was present. During vitrectomy and under scleral indentation at 5-o'clock position, a cilium was found at far retinal periphery. One end of the cilium was embedded in the retina, whereas the other end floated freely in the vitreous. The cilium was removed through the pars plana sclerotomy with intraocular foreign body forceps. The procedure was completed without any complications. CONCLUSION: Penetrating eye injury is the most possible cause of cilium entrance in vitreous cavity in this case, which suggests that cilium can be well tolerated in vitreous cavity for as long as 40 years.

Optical Coherence Tomography Angiography Changes in Patients Diagnosed With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to assess the association between optical coherence tomography angiography (OCTA) parameters and acute coronary syndrome (ACS). Two independent reviewers searched the electronic databases (MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, Embase (Excerpta Medica Database), Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform) from inception until April 2023. According to the inclusion criteria of this review, eligible were observational studies, randomized control trials, and registry/database studies that included the eyes of adult ACS patients and assessed OCTA parameters within the macula. The pooled standardized mean differences (SMD) between patients diagnosed with ACS and healthy controls with a confidence interval (CI) of 95% were calculated using the Hartung-Knapp-Sidik-Jonkman random-effects method. The heterogeneity was assessed by I2 and the Cochran Q and a random effects model was applied. Seven studies were eligible and included in our systematic review (n = 898), of which three were included in the meta-analysis (n = 341). The pooled SMD in the superficial vascular plexus (SVP), deep vascular plexus (DVP), and foveal avascular zone (FAZ) were -0.46 (95% CI: -0.94 to 0.01, p = 0.05, I2 = 0%, three studies), -0.10 (95% CI: -3.20 to 3.00, p = 0.75, I2 = 67%, two studies), and 0.43 (95% CI: -1.22 to 2.09, p = 0.38, I2 = 92%, three studies), respectively. Our findings suggest that there are no differences in OCTA metrics between ACS patients and healthy individuals.

Gentamicin-induced macular toxicity in 25-gauge sutureless vitrectomy.

We report a case of a 52-year-old man who developed superficial and intraretinal hemorrhages, retinal edema and extensive cotton-wool patches, 2 weeks after the subconjuctival injection of gentamicin at the end of a 25 gauge sutureless vitrectomy (pars plana vitrectomy) for the repair of a, macula on, retinal detachment in his left eye. Fluorescein angiography revealed sharply defined zones of retinal vascular non-perfusion, mostly confined to the posterior pole and visual acuity deteriorated to 1/20 and remained unchanged during the follow up time. Our case illustrates the possibility of aminoglycoside toxicity after 25-gauge transconjunctaval sutureless PPV when the latter is administered subconjuctivally. It emphasizes that less toxic subconjuctival antibiotics may be considered for sutureless surgery, since if aminoglycoside toxicity occurs, the patient's vision may be permanently affected.

Correlation Between Coronary and Retinal Microangiopathy in Patients With STEMI.

Purpose: To investigate the morphological and functional correlation between microvascular retinal changes in optical coherence tomography angiography (OCTA) and the microvascular coronary circulation in patients with ST elevation myocardial infarction (STEMI) coronary heart disease (CHD). Methods: A total of 330 eyes from 165 participants (88 cases and 77 controls) were enrolled and imaged. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vascular density was measured in the central (1 mm) and perifoveal (1-3 mm) areas and in the superficial foveal avascular zone (FAZ) and choriocapillaris (3 mm). These parameters were then correlated to the left ventricular ejection fraction (LVEF), and the number of affected coronary arteries. Results: Decreased vessel densities in the SCP and DCP and choriocapillaris were positively correlated to the LVEF values (P = 0.006, P = 0.026, and P = 0.002, respectively). No statistically significant correlation between the SCP and DCP central area or FAZ area was found. Regarding the number of affected vessels, significant negative correlations were revealed for the SCP and DCP central vessel densities (P < 0.001 and P < 0.001, respectively) and the SCP perifoveal vascular density (P = 0.009). Conclusions: OCTA vascular indices are significantly correlated with morphological and functional parameters in patients with STEMI CHD. SCP vascular density especially seems to be a promising biomarker for the extent of both macrovascular damage (number of affected coronary arteries) and microvascular damage, as mirrored in the decreased LVEF at admission. Translational Relevance: OCTA vascular indices offer a valuable insight into the microvascular status of coronary circulation.

Morphometric analysis of fibrovascular pigment epithelial detachments treated with ranibizumab and aflibercept.

PURPOSE: To assess fibrovascular pigment epithelial detachments (PED) and their response to two different anti-VEGF agents using optical coherence tomography (OCT) morphometric analysis. METHODS: Seventy-three consecutive, treatment-naïve eyes with fibrovascular PED (>125 µm) treated with ranibizumab or aflibercept were retrospectively included. A custom-made software was used to manually segment and calculate PED maximum height, base area, volume and internal reflectivity at baseline, after three injections and 1 year. RESULTS: Visual acuity (VA) change was 2 ETDRS letters ± 7.6 after three injections and 3.2 ETDRS letters ± 10.3 at 1 year. There was no significant difference between VA changes amongst the two drugs. At 1 year, anti-VEGF treatment resulted in a mean reduction of 125 µm in maximum PED height, of 2.26 mm2 in base area and of 0.54 mm3 in volume with a corresponding increase in reflectivity. These changes were more prominent in the aflilbercept group. The observed PED and VA changes at year 1 were strongly correlated with their values at baseline and after three injections. CONCLUSIONS: Anti-VEGF treatment resulted in a reduction of all PED dimensions and a corresponding increase in optical reflectivity. Higher, larger and more hypo-reflective PEDs demonstrated a better anatomical response, especially with aflibercept, but this was not correlated with VA.

Sustained ocular hypertension following intravitreal injections of 0.5 mg/0.05 ml ranibizumab.

To report three cases with sustained ocular hypertension following intravitreal injections of 0.5 mg/0.05 ml ranibizumab and to underline the importance of monitoring intraocular pressure (IOP) following intravitreal injections of ranibizumab (Lucentis). Three patients were found to have high IOP after intravitreal injections of 0.5 mg/0.05 ml ranibizumab. IOP was elevated after the second ranibizumab injection in patients 1 and 2, and after the third injection in patient 3. The increase in IOP was sustained, requiring treatment with anti-glaucoma eye drops in all patients, the addition of systemic carbonic anhydrase inhibitor in one patient, and the application of selective laser trabeculoplasty (SLT) in another patient. None of the patients had a previous history of glaucoma or ocular hypertension. Sustained ocular hypertension may occur after intravitreal injections of 0.5 mg/0.05 ml ranibizumab. Although the precise mechanism of the pressure rise is unknown, three eyes in our series were controlled with topical or oral medication and one with SLT. The necessity of IOP monitoring is strongly emphasized after intravitreal injections of 0.5 mg/0.05 ml ranibizumab.

Correlation Between Central Corneal Thickness and Radial Peripapillary Capillary Density, in Patients With Ocular Hypertension.

Purpose To investigate any possible relationship between the central corneal thickness and the radial peripapillary capillary density detected by optical coherence tomography (OCT) angiography in eyes with ocular hypertension. Materials and methods In this observational study, 135 eyes were examined. OCT angiography of the optic disc (4.5 mm) and ultrasound corneal pachymetry were performed in all cases. Age, medical treatment for ocular hypertension, sex, and retinal nerve fiber layer thickness were evaluated. The main indices of blood flow were also examined. Spearman correlation coefficients were used to explore the association between two continuous variables. Results A directly proportional significance regarding the correlation between central corneal thickness and radial peripapillary network was indicated in eyes with ocular hypertension (p = .036). Conclusions Central corneal thickness and radial peripapillary capillary density constitute two essential screening parameters for patients with ocular hypertension.

Retinal Pigment Epithelial Detachment in Age-Related Macular Degeneration.

Retinal pigment epithelial detachment is defined as a separation of the retinal pigment epithelium from the inner collagenous layer of Bruch's membrane. It is a common manifestation in both dry and wet types of age-related macular degeneration. This review aims to provide a comprehensive guide to the pathophysiology, clinical and imaging characteristics, natural course and treatment of the various types of pigment epithelial detachments in order to assist in diagnosis and management of this important feature of age-related macular degeneration.

NOTCH3 and CADASIL syndrome: a genetic and structural overview.

CADASIL syndrome is a rare disease that belongs to a group of disorders called leukodystrophies. It is well established that NOTCH3 gene on chromosome 19 is primarily responsible for the development of the CADASIL syndrome. Herein, an attempt is made to shed light on the actual molecular mechanism underlying CADASIL syndrome, through insights extracted from comprehensive evolutionary studies and in silico modelling on Notch 3 protein. In particular, we suggest the use of optical coherence tomography angiography for the detection of early signs of small vessel diseases, which are the major precursors to a repertoire of neurodegenerative conditions, including CADASIL.