OCT biomarkers as predictors of visual improvement in diabetic macular edema eyes receiving dexamethasone implants.

BACKGROUND: Several optical coherence tomography (OCT) biomarkers have been proposed as predictors for functional and anatomical outcomes in Diabetic Macular Edema (DME). This study aims to examine the impact of these OCT features on the visual acuity improvement of patients with DME after long-acting Dexamethasone intravitreal implants (DEX-I) injection. Furthermore, the safety and impact of DEX-I on clinical parameters, including intraocular pressure (IOP) were assessed. METHODS: In this retrospective observational study, we reviewed the medical records of naïve and non-naïve eyes with DME who received at least one DEX-I. The primary endpoint was visual acuity improvement of ≥ 5 ETDRS letters at 1 month and 4 months after treatment. Secondary outcomes were the changes in OCT biomarkers and the impact of DEX-I on IOP at 1 and 4 months of follow-up. Linear panel regression analysis was used to test for differences in central subfield thickness (CST) over time and it was stratified according to biomarkers at baseline. Finally, a logistic regression analysis was used to identify factors predicting visual improvement at 1 and 4 months. RESULTS: We included 33 eyes of which 63.6% were at an advanced stage of DME. Overall, CST, cube average thickness (CAT), cube volume (CV), and intraretinal cystoid spaces > 200 µm (ICS) decreased following DEX-I injection (p < 0.001). Additionally, a thicker CST at baseline was observed in eyes with better visual improvement at one month (p = 0.048). After logistic regression analysis, CST was retained as the only predictor for visual improvement at one month (p = 0.044). Furthermore, panel regression analysis identified a relation between subfoveal neuroretinal detachment (SND) at baseline and CST increase at four months. Lastly, only 15.2% of the eyes necessitated topical medication for IOP reduction, with no differences observed when stratifying between naïve and non-naïve eyes. CONCLUSION: Our analyses suggest that a ticker baseline CST may serve as a positive predictor of early visual improvement and SND presence at baseline may be a negative prognostic factor for CST increase 4 months after DEX-I injection. Other well-known biomarkers, such as disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HF), did not demonstrate prognostic value on visual outcomes, at least within the first four months following the injection.

Management of Spontaneous Crystalline Lens Luxation in a Patient Diagnosed with Takayasu's Disease.

Takayasu's disease is a chronic granulomatous arteriopathy that affects large vessels and their major branches. Nonspecific symptoms characterize the early phase, whereas findings of arterial occlusion and aneurysmal formation become manifest later. Ocular signs typically refer to retinal vascular involvement, as Takayasu arteritis or hypertensive retinopathy. We report a case of a 63-year-old woman suffering from Takayasu arteritis that complained of sudden onset of blurred vision in her left eye due to crystalline lens luxation in the vitreous cavity. The patient's past medical history was unremarkable for trauma, personal or familiar collagenopathies. Prompt surgical management was performed and the patient reached 0 LogMAR seven days after surgery. Our case illustrates the concomitant occurrence, never reported before, of two rare conditions in the same patient, namely, Takayasu arteritis and spontaneous lens dislocation. Further research and future knowledge are needed to explain whether Takayasu arteritis could obliquely injure zonular or fibrillar structures and whether these features may be possibly related.

Correlation between Morphological Characteristics of Macular Edema and Visual Acuity in Young Patients with Idiopathic Intermediate Uveitis.

Background and Objectives: Macular edema (ME) is a common complication of intermediate uveitis (IU). It is often responsible for a decrease in visual acuity (VA). Three distinct patterns of macular edema have been described in intermediate uveitis, namely, cystoid macular edema (CME), diffuse macular edema (DME), and serous retinal detachment (SRD). The current study aims to describe the characteristics of macular edema in young patients with idiopathic intermediate uveitis and to correlate its features with VA using spectral domain optical coherence tomography (SD-OCT). Materials and Methods: A total of 27 eyes from 18 patients with idiopathic IU complicated by ME were included in this retrospective study. All patients underwent SD-OCT; data were gathered at the onset of ME. Best-corrected VA (BCVA) was correlated with the morphological features of ME. Results: BCVA was negatively correlated with Ellipsoid Zone (EZ) disruption (p = 0.00021), cystoid pattern (p = 0.00021), central subfield thickness (CST) (p < 0.001), and serous retinal detachment (0.037). Conclusions: In ME secondary to idiopathic IU, VA negatively correlates with Ellipsoid Zone disruption and increases in CST. Moreover, vision is influenced by the presence of cysts in the inner nuclear and outer nuclear layers and by the neuroepithelium detachment.

Beta-Amyloid Peptide in Tears: An Early Diagnostic Marker of Alzheimer's Disease Correlated with Choroidal Thickness.

We aimed to evaluate the diagnostic role of Alzheimer's disease (AD) biomarkers in tears as well as their association with retinal and choroidal microstructures. In a cross-sectional study, 35 subjects (age 71.7 ± 6.9 years) were included: 11 with prodromal AD (MCI), 10 with mild-to-moderate AD, and 14 healthy controls. The diagnosis of AD and MCI was confirmed according to a complete neuropsychological evaluation and PET or MRI imaging. After tear sample collection, ß-amyloid peptide Aß1-42 concentration was analyzed using ELISA, whereas C-terminal fragments of the amyloid precursor protein (APP-CTF) and phosphorylated tau (p-tau) were assessed by Western blot. Retinal layers and choroidal thickness (CT) were acquired by spectral-domain optical coherence tomography (SD-OCT). Aß1-42 levels in tears were able to detect both MCI and AD patients with a specificity of 93% and a sensitivity of 81% (AUC = 0.91). Tear levels of Aß1-42 were lower, both in the MCI (p < 0.01) and in the AD group (p < 0.001) when compared to healthy controls. Further, Aß1-42 was correlated with psychometric scores (p < 0.001) and CT (p < 0.01). CT was thinner in the affected patients (p = 0.035). No differences were observed for APP-CTF and p-tau relative abundance in tears. Testing Aß1-42 levels in tears seems to be a minimally invasive, cost-saving method for early detection and diagnosis of AD.

Cocaine Abuse as an Immunological Trigger in a Case Diagnosed with Eales Disease.

Background: Eales disease is a clinical syndrome affecting the mid-peripheral retina with an idiopathic occlusive vasculitis and possible subsequent retinal neovascularization. The disease can develop into visually threatening complications. Case Presentation: We report the case of a 40-year-old Caucasian male with a history of cocaine abuse who presented with blurred vision in the left eye (LE). Fundus examination showed vitreous hemorrhages, peripheral sheathing of venous blood vessels, areas of retinal neovascularization in the LE, and peripheral occlusive phlebitis in the right eye. The full serologic panel was negative except for the heterozygous mutation of factor V Leiden. Clinical and biochemical parameters suggested a diagnosis of Eales disease. Therapy with dexamethasone, 1 mg per kg per day, tapered down slowly over 4 months, and peripheral laser photocoagulation allowed a regression of clinical signs and symptoms. Conclusion: This case shows an uncommon presentation of Eales disease associated with cocaine abuse. Both cocaine abuse and a thrombophilic pattern, as cofactors, might have sensitized the retinal microcirculation on the pathogenetic route to this retinal pathology. Furthermore, in view of this hypothesis, a thorough ocular and general medical history investigating drug abuse and coagulation disorders is recommended for ophthalmologists in such cases.

Choroidal Effusion with Exudative Retinal Detachment following Non Perforating YAG-Laser Peripheral Iridotomy: A Case Report.

AIM: To report a case of choroidal effusion and exudative retinal detachment following a non perforating Yttrium-Aluminium-Garnett (YAG)-laser iridotomy. DESIGN: Case report. METHODS: A 53-year-old woman complains of sudden onset of blurred vision in her left eye 15 days after the attempt of YAG-laser peripheral iridotomy. Clinical examination revealed 3+ flare and 1+ cells in the anterior chamber, 2+ vitreous cells, swollen optic nerve, ciliochoroidal effusion, and exudative retinal detachment involving macular area in the left eye. After starting treatment with prednisone 25 mg once daily, choroidal effusion and retinal detachment were managed successfully without any surgical approach. CONCLUSION: Serous choroidal and exudative retinal detachments are rare complications following YAG-laser procedure. In our case, this clinical presentation occurs after a non perforating iridotomy. In medical practice, exudative retinal detachment should be always considered after YAG-laser iridotomy.

Does choroidal thickness predict persistent subretinal fluid after rhegmatogenous retinal detachment repair? A retrospective study with fellow eye comparison.

PURPOSE: To evaluate whether choroidal thickness (CT) is associated with persistent subretinal fluid (pSRF) after simple primary rhegmatogenous retinal detachment (RRD) repair. METHODS: This single-centre, retrospective, observational study included patients who underwent RRD repair with at least 12-month follow-up. Preoperative and postoperative parameters were evaluated for association with pSRF. CT measurements were obtained at the central 1 mm area on enhanced depth imaging (EDI) OCT scans, using a semiautomatic method. Multiple logistic regression analyses were assessed to determine predictive factors for pSRF. RESULTS: Overall, 100 eyes of 100 patients, mean age of 59.9 ± 12.6 years were included. pSRF was found in 21.0% of eyes and resolved over time in 85.7% of eyes at 12 months. In the pSRF group both RRD and fellow eyes showed lower mean choroidal and RPE thickness values as compared to those without pSRF (p < 0.05). A significant correlation was found between pSRF occurrence and choroidal thinning (p = 0.02). After multiple regression analyses, macula-off RRD (p = 0.005) and scleral buckling (SB) technique (p = 0.001) were retained as final predictors for pSRF. In macula-off SB eyes, detachment duration was the only factor associated with pSRF (p = 0.046). There were no significant differences in best-corrected visual acuity outcomes between the pSRF and the no-pSRF eyes. CONCLUSIONS: Patients with pSRF showed lower choroidal and RPE thickness as compared to those without pSRF. CT did not turn out to be a final predictor for pSRF, as this was mainly associated with macular involvement, surgical technique and detachment duration.

COMPARISON BETWEEN SCLERAL BUCKLING AND VITRECTOMY IN THE ONSET OF CYSTOID MACULAR EDEMA AND EPIRETINAL MEMBRANE AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To investigate the incidence and risk factors for the main complications in patients with rhegmatogenous retinal detachment treated with scleral buckling (SB) or pars plana vitrectomy (PPV). METHODS: A retrospective, comparative, observational study was conducted. The medical records of 107 patients with primary rhegmatogenous retinal detachment who were managed with SB (n = 57) or PPV (n = 50) were reviewed. Scleral buckling was performed using scleral encircling solid silicone band and circumferential solid silicone exoplant to support the break. Pars plana vitrectomy was combined with phacoemulsification in phakic eyes and with scleral encircling in inferior detachments. Follow-ups, including spectral-domain optical coherence tomography examination, were scheduled at 1, 3, and 12 months after surgery. Propensity score matching was used to adjust for potential preoperative selection bias. RESULTS: The overall incidence of postoperative cystoid macular edema (CME) and epiretinal membrane was 14.95% and 30.84%, respectively. Compared with SB, CME was more frequent in the PPV (P = 0.021) and in the PPV pseudophakic eyes (P = 0.027). Postoperative CME was an early, predominantly transient complication and regressed in 67% of SB and in 77% of PPV eyes within 12 months after surgery. No differences were observed regarding epiretinal membrane development. Except for the surgical technique, no preoperative factors associated with CME were identified. A correlation between epiretinal membrane and patients' age was found (P = 0.028). CONCLUSION: The incidence of CME after rhegmatogenous retinal detachment repair was higher in patients who underwent PPV, either alone or combined with phacoemulsification, than in those treated with SB. Epiretinal membrane development was correlated to older age, regardless of the surgical procedure.

Complement Mediators in Development to Treat Age-Related Macular Degeneration.

Over recent years, great attention has been paid to the role of the complement system in the pathogenesis of age-related macular degeneration (AMD). In particular, several studies have highlighted a link between AMD development and complement dysregulation, which can probably be explained as a complement cascade hyperactivation resulting from the presence of a series of risk factors such as aging; smoking; obesity; alcohol consumption; exposure to pesticides, industrial chemicals, or pollution; and other causes of oxidative stress. This hypothesis has been mainly supported by the presence of complement mediators as constituents of drusen, representing one of the earliest and most characteristic signs of retinal damage in AMD. Additionally, activated complement mediators and some complement regulators, such as vitronectin, have been found not only in the drusen and adjacent retinal areas but also in the peripheral blood of patients with AMD. Therefore, we aim to provide a review of recently studied complement factors to highlight their role in the pathogenesis of AMD and to evaluate new potential therapeutic strategies.

Ten-Year Outcomes of Intravitreal Bevacizumab for Myopic Choroidal Neovascularization: Analysis of Prognostic Factors.

The current standard treatment of myopic choroidal neovascularisation (mCNV) is intravitreal injection of VEGF antagonists. This study was proposed to assess efficacy and safety of intravitreal bevacizumab (IVB) for the treatment of mCNV across a 10-year follow-up. Thirty eyes of thirty patients with treatment-naïve mCNV who underwent IVB and were followed up with for a minimum of ten years were recruited for the present retrospective cohort study. All participants were treated with three monthly IVB at baseline and then evaluated and treated under pro re nata (PRN) schedule. Outcome measures were to determine BCVA changes over years and identify the predictive factors of both final visual outcome and need for retreatment. Analysis of the main involved prognostic factors with correlations among variables is reported. Visual acuity remained stable at 10-year follow-up (p = 0.001) with the greatest improvement at 2 years (p < 0.0001) in all CNV locations. Baseline BCVA correlated positively with final BCVA (ß = 0.88, p < 0.0001, R2: 0.75). No predictive factors for the need of additional injections were identified. Retinal and choroidal thickness significantly reduced over time but without correlation with the number of injections. CNV max height and area significantly decreased at 10 years (p < 0.0001 and p = 0.003, respectively), with complete regression of mCNV lesion in 40% of subjects. Intravitreal bevacizumab resulted as long-term effective and safe therapy for mCNV with sustained results at 10 years.

Recent Advances and Disputes About Curcumin in Retinal Diseases.

Curcumin belongs to the group of so-called phytocompounds, biologically active molecules produced by plants exerting a beneficial effect on health. Curcumin shows a wide spectrum of different properties, being an anti-inflammatory, antioxidant, antimicrobial and antimutagenic molecule. The purpose of the review is to examine what literature reported on the characteristics of curcumin, particularly, on the beneficial and controversial aspects of this molecule, aiming for a better therapeutic management of retinal diseases. The retina is a constant target of oxidative stress, this tissue being characterized by cells rich in mitochondria and by vessels and being, obviously, continuously reached from photons affecting its layers. Particularly, the retinal ganglion cells and the photoreceptors are extremely sensitive to oxidative stress damage and it is well known that an imbalance in reactive oxygen species is often involved in several retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, central serous chorioretinopathy, macular edema, retinal ischemia-reperfusion injury, proliferative vitreoretinopathy, hereditary tapeto-retinal degenerations, and retinal and choroidal tumors. To date, several studies suggest that oral treatment with curcumin is generally well tolerated in humans and, in addition, it seems to have no negative effects: therefore, curcumin is a promising candidate as a retinal disease therapy. Unfortunately, the primary limitation of curcumin is represented by its poor bioavailability, in fact only a minimal fraction of this substance can reach the blood stream in the form of a biologically active compound. However, many steps have been made in several fields. In the future, it is expected that the strategies developed until now to allow curcumin to reach the target tissues in adequate concentrations could be ameliorated and, above all, large in vivo studies on humans are needed to demonstrate the total safety of these compounds and their effectiveness in different eye diseases.

Long-term ocular biometric variations after scleral buckling surgery in macula-on rhegmatogenous retinal detachment.

BACKGROUND: Myopic shift and biometric ocular changes have been previously observed after scleral buckling (SB) surgery in rhegmatogenous retinal detachment (RRD), but long term-term outcomes had not yet been explored. The purpose of present study is to evaluate long term ocular biometric changes in patients with primary macula-on RRD treated with SB. METHODS: In this retrospective, observational study, we reviewed the medical records of patients undergoing SB surgery for macula-on RRD. Ocular biometry was performed before and at the most recent visit after surgery. Axial length (AXL), anterior chamber depth (ACD), anterior corneal astigmatism and spherical equivalent in treated eyes were compared before and after surgery as well as with those of fellow eyes. RESULTS: Thirty-four eyes of 17 patients with a mean age of 57.0 ± 8.9 years were included. The mean follow-up duration was 50.9 ± 21.9 months (median 53.0; range 12 to 82 months). A significant postoperative AXL increase of 0.83 mm and a concomitant myopic shift of 1.35 diopters was observed in the operated eyes (p <  0.0001). The preoperative AXL was the only predictive factor of AXL change after surgery (B = 0.152, 95% CI 0.059 to 0.245, ß = 0.668, P = 0.003). Compared to fellow eyes, a postoperative ACD shallowing of 0.1 mm was found in operated eyes (p <  0.05), while there were no long-term changes of anterior corneal astigmatism. CONCLUSIONS: We show that the preoperative AXL is the only predictive factor of AXL increase after SB surgery. Scleral encircling induces a concomitant long-term shallowing of the AC, therefore fourth generation intraocular lens (IOL) power calculation formulae should be used for patients requiring cataract surgery after SB.

Involvement of ocular surface in graft-versus-host disease: An update from immunopathogenesis to treatment.

Graft-versus-host disease is a common complication of hematopoietic stem cell transplantation and the ocular surface is a main target of inflammatory reaction.

Retinal involvement and ocular findings in COVID-19 pneumonia patients.

Changes in immune and coagulation systems and possible viral spread through the blood-brain barrier have been described in SARS-CoV-2 infection. In this study, we evaluated the possible retinal involvement and ocular findings in severe COVID-19 pneumonia patients. A cross-sectional study was conducted on 46 patients affected by severe COVID-19 who were hospitalized in one intensive care unit (ICU) and in two infectious disease wards, including bedside eye screening, corneal sensitivity assessment and retinography. A total of 43 SARS-CoV-2-positive pneumonia patients affected with COVID-19 pneumonia were included, including 25 males and 18 females, with a median age of 70 years [IQR 59-78]. Except for one patient with unilateral posterior chorioretinitis of opportunistic origin, of whom aqueous tap was negative for SARS-CoV-2, no further retinal manifestation related to COVID-19 infection was found in our cohort. We found 3 patients (7%) with bilateral conjunctivitis in whom PCR analysis on conjunctival swabs provided negative results for SARS-CoV-2. No alterations in corneal sensitivity were found. We demonstrated the absence of retinal involvement in SARS-CoV-2 pneumonia patients. Ophthalmologic evaluation in COVID-19, particularly in patients hospitalized in an ICU setting, may be useful to reveal systemic co-infections by opportunistic pathogens.

Macular Ganglion Cell Layer Thickness after Macula-Off Rhegmatogenous Retinal Detachment Repair: Scleral Buckling versus Pars Plana Vitrectomy.

(1) Background: We evaluated macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness in patients with primary macula-off rhegmatogenous retinal detachment (RRD) treated with scleral buckling (SB) or pars plana vitrectomy (PPV) using spectral domain optical coherence tomography (SD-OCT). (2) Methods: In this retrospective, observational study, we reviewed the medical records of patients undergoing SB or PPV surgery for macula-off RRD. SD-OCT was performed at three and 12 months after surgery. The central and parafoveal GCL-IPL thicknesses in treated eyes were compared with those of healthy fellow eyes. OCT measurements between the SB and PPV group were also compared using the analysis of covariance. (3) Results: Seventy-one eyes of 71 patients with a mean age of 61.2 ± 11.7 years were included. The parafoveal GCL-IPL thickness of the PPV group was significantly reduced, with respect to fellow eyes, at three and 12 months (p < 0.01). After adjusting for age, axial length, spherical equivalent, RD extent, preoperative intraretinal cysts, duration of symptoms and postoperative IOP, the parafoveal GCL-IPL thickness in the PPV group was significantly reduced with respect to the SB group, both at three and 12 months (F = 11.45, p = 0.001 and F = 12.37, p = 0.001, respectively). (4) Conclusions: In conclusion, the GCL-IPL is reduced in thickness in eyes with macula-off RRD treated with vitrectomy and is significantly thinner compared to eyes undergoing scleral buckling surgery.

High myopic patients with and without foveoschisis: morphological and functional characteristics.

PURPOSE: Myopic foveoschisis (MF) is characterized by the splitting of the retinal layers in the fovea of patients with high myopia (HM). MF may progress into foveal detachment or macular hole formation with consequent loss of central vision. The aim of this study is to investigate morphological and functional changes of the macular region in myopic subjects with and without foveoschisis. DESIGN: Observational, cross-sectional, comparative study. METHODS: Forty-eight patients with HM and 24 healthy controls were evaluated by spectral domain-optical coherence tomography (SD-OCT), multifocal electroretinography (mfERG) and microperimetry (MP-1) tests to assess macular thickness, functionality and sensitivity values, respectively. The results of the diagnostic examinations were compared between three groups: HM patients with MF (N = 24), HM patients without MF (N = 24) and control group (CG) (N = 24). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). One-way analysis of variance (ANOVA) followed by Tukey's post hoc test was used to analyze differences between groups unless specified; p values < 0.05 were considered as statistically significant. Gender distribution was compared by the Chi square test. RESULTS: The statistical analysis with one-way ANOVA followed by Tukey's post hoc test showed a significant increase in macular thickness in HM patients with MF when compared to both HM patients without MF and CG. Morphological changes were associated with functional impairment as demonstrated by the significant decrease in amplitude of the P1 wave and MP-1 sensitivity (p < 0.05), according to the anatomical landmarks. CONCLUSIONS: This study showed that the morphological changes observed in the central retina of HM patients with MF are associated with functional alterations. High-tech diagnostic tests such as SD-OCT, mfERG and MP-1 could be useful for management in complications of MF.

Self-sealing posterior scleral perforation in airgun ocular trauma, surgical tip: a case report.

BACKGROUND: Intraorbital metallic foreign bodies have varied clinical presentations. Here, we report the unusual case of intraoperative evidence of spontaneously healed posterior scleral perforation in a severe ballistic trauma without previous instrumental signs of penetrating wound and complete visual restoration after surgery. CASE PRESENTATION: The patient was hit by several lead hunting pellets in the chest, abdomen, limbs, face and orbit. Computed Tomography (CT) images revealed the presence of a pellet within the orbitary cavity, close to the optic nerve, with no signs of penetrating ocular wound. While performing vitrectomy for severe vitreous hemorrhage, a point of strong adherence between a old hemorrhage and retinal surface was identified and managed conservatively, as it was attributed to trauma related-impact area. So, lead foreign body took an unusual trajectory impacting the globe and finally lodging back in the deep orbitary cavity, in absence of significant ocular injury and with visual prognosis preservation. CONCLUSIONS: Our findings provide further information on orbital injuries from airguns, a theme of growing popularity and concern. Intraoperative recognition of hardly removable old hemorrhagic clot as self-blockage site of posterior scleral penetrating trauma, allowed for surgical stabilization and minimal solicitation of the area to avoid inadvertent perforation.

Anti-Vascular Endothelial Growth Factor Intravitreal Therapy and Macular Ganglion Cell Layer Thickness in Patients with Neovascular Age-Related Macular Degeneration.

Purpose: To assess macular ganglion cell layer (GCL) thickness in patients treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for exudative age-related macular degeneration (AMD). Materials and Methods: This was a two-year retrospective institutional case series where records of patients treated with anti-VEGF injections for unilateral AMD were reviewed for BCVA, intraocular pressure, and spectral domain optical coherence tomography. Macular GCL thickness was evaluated with automated retinal segmentation based on ETDRS grid rings. Retinal layer segmentation was carefully assessed and manually corrected for any misalignment. Results: 48 eyes of 24 patients with unilateral exudative AMD were included. The mean number of anti-VEGF injections was 10.4 ± 3.2. Fellow eyes were classified as AREDS category one and two. There was significant thinning of the 3-mm macular GCL in treated compared with fellow eyes at one and two years (P = .03 and P = .04, respectively). GCL thickness compared to baseline showed a significant decrease at one and two years in treated (P = .01 and <0.0001) and at two years in untreated fellow eyes (P = .02). Conclusions: There is a decrease of macular GCL thickness in eyes with exudative AMD treated with anti-VEGF intravitreal injections in comparison with fellow eyes. There is longitudinal thinning of the GCL from baseline in eyes with both treated exudative and non-treated early AMD.

Optical coherence tomography evidence of macular ganglion cell-inner plexiform layer thinning in eyes with subretinal drusenoid deposits.

BACKGROUND/OBJECTIVES: The purpose of this study was to evaluate macular ganglion cell layer-inner plexiform layer (GCL-IPL) and choroidal thickness in early age-related macular degeneration (AMD) in eyes with subretinal drusenoid deposits (SDD). SUBJECTS/METHODS: Comprehensive ophthalmological examination was performed. Near infrared reflectance and raster images using enhanced depth imaging were acquired with spectral domain optical coherence tomography. Drusen and SDD were diagnosed based on raster scans and near infrared reflectance. GCL-IPL maps were generated with automated segmentation and choroidal thickness maps were obtained by manually delineating the choroid-scleral boundary. RESULTS: Forty-eight eyes from 48 patients (mean age 77.5 ± 5.7, range 68-90 years) with a diagnosis of early AMD and 42 eyes of 42 age-matched control subjects (mean age 76.9 ± 5.7, range 67-88 years) were included. Of these, 28 eyes (58.3%) had drusen alone, 4 eyes (8.3%) had SDD alone, and 16 eyes (33.3%) had drusen associated with SDD. Compared with controls, average choroidal thickness was significantly decreased in AMD eyes (P < 0.05). There was no significant difference in choroidal thickness in eyes with SDD with respect to those with drusen alone. GCL-IPL thickness was reduced in an annular pattern at the 3 and 6 mm macular areas in AMD patients with respect to controls (P < 0.05). GCL-IPL thickness at 3 mm was significantly reduced in eyes with SDD with respect to those with drusen alone (P = 0.03). CONCLUSIONS: The GCL-IPL is reduced in thickness with an annular pattern in early AMD and is significantly thinner in eyes with SDD.

VEGF inhibition alters neurotrophin signalling pathways and induces caspase-3 activation and autophagy in rabbit retina.

This study sought to evaluate the prospective role exerted by vascular endothelial growth factor (VEGF) in the modulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) signalling pathways in the rabbit retina. To reach this aim, the anti-VEGF agents aflibercept and ranibizumab were used as a pharmacological approach to evaluate the putative consequences elicited by VEGF inhibition on neurotrophin signalling. VEGF inhibition determined a marked imbalance in proneurotrophin expression, a significant reduction in TrkA and TrkB phosphorylation states and a decrease in the pan-neurotrophin receptor p75. Importantly, VEGF blockade also caused a strong increase in cleaved caspase-3, beclin-1 and lipidated LC3. The effects were more pronounced in the aflibercept group when compared with ranibizumab-treated rabbits, particularly 1 week after injection. This study demonstrates that VEGF exerts pivotal physiological roles in regulating NGF and BDNF pathways in the retina, as its inhibition by anti-VEGF agents deeply impacts neurotrophin homeostasis. These events are accompanied by a sustained induction of apoptotic and autophagic markers, suggesting that anti-VEGF-dependent impairments in neurotrophin signalling could be responsible for the activation of retinal cell death pathways.