RETINAL TECTONICS AFTER MACULAR PUCKER SURGERY: Thickness Changes and En Face Displacement Recovery.

PURPOSE: To study visual function, retinal layer thickness changes, and tangential displacement after pars plana vitrectomy for epiretinal membrane. METHODS: Retrospective series of patients undergoing pars plana vitrectomy for epiretinal membrane, with 6-month follow-up including best-corrected visual acuity, optical coherence tomography, M-charts, epiretinal membrane grading, and infrared fundus photograph at time 0 (T0, preop) at months 1 (T1), 3 (T3), and 6 (T6) postop (±1 week). Retinal layer thickness and tangential ( en face ) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En face displacement was calculated as optical flow of consecutive images. RESULTS: Average best-corrected visual acuity improved from 0.28 ± 0.08 logarithm of Minimum Angle of Resolution at T0 to 0.16 ± 0.25 at T6 ( P = 0.05), best-corrected visual acuity improvement correlated with best corrected visual acuity (BCVA) at T0 ( P < 0.001). Vertical metamorphopsia decreased from 1.33° ± 0.70° at T0 to 0.82° ± 0.69° at T6 ( P < 0.05). Foveal thickness reduced from 453 ± 53 µ m at T0 to 359 ± 31 µ m at T6 ( P < 0.05) and reduction correlated with best-corrected visual acuity improvement ( P < 0.05). Foveal layers decreased ( P < 0.05) in all cases. The mean en face deformation was 155.82 ± 50.17 µ m and mostly occurred in the first month: T0-T1 displacement was 83.59 ± 30.28 µ m, T1-T3 was 36.28 ± 14.45 µ m, while T3-T6 was 39.11 ± 22.79 µ m ( P < 0.001) on average. Perifoveal and parafoveal deformation correlated with optical coherence tomography foveal thickness reduction at all time intervals (1, 3, and 6 months: P < 0.01). CONCLUSION: Epiretinal membrane peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en face and in-depth changes correlate with visual function.

TLR2 and TLR4 Are Expressed in Epiretinal Membranes: Possible Links with Vitreous Levels of Complement Fragments and DAMP-Related Proteins.

Previous studies reported the expression of toll-like receptors (TLRs), merely TLR2 and TLR4, and complement fragments (C3a, C5b9) in vitreoretinal disorders. Other than pathogens, TLRs can recognize endogenous products of tissue remodeling as damage-associated molecular pattern (DAMPs). The aim of this study was to confirm the expression of TLR2 and TLR4 in the fibrocellular membranes and vitreal fluids (soluble TLRs) of patients suffering of epiretinal membranes (ERMs) and assess their association with disease severity, complement fragments and inflammatory profiles. Twenty (n = 20) ERMs and twelve (n = 12) vitreous samples were collected at the time of the vitrectomy. Different severity-staged ERMs were processed for: immunolocalization (IF), transcriptomic (RT-PCR) and proteomics (ELISA, IP/WB, Protein Chip Array) analysis. The investigation of targets included TLR2, TLR4, C3a, C5b9, a few selected inflammatory biomarkers (Eotaxin-2, Rantes, Vascular Endothelial Growth Factor (VEGFA), Vascular Endothelial Growth Factor receptor (VEGFR2), Interferon-γ (IFNγ), Interleukin (IL1ß, IL12p40/p70)) and a restricted panel of matrix enzymes (Matrix metalloproteinases (MMPs)/Tissue Inhibitor of Metallo-Proteinases (TIMPs)). A reduced cellularity was observed as function of ERM severity. TLR2, TLR4 and myD88 transcripts/proteins were detected in membranes and decreased upon disease severity. The levels of soluble TLR2 and TLR4, as well as C3a, C5b9, Eotaxin-2, Rantes, VEGFA, VEGFR2, IFNγ, IL1ß, IL12p40/p70, MMP7 and TIMP2 levels were changed in vitreal samples. Significant correlations were observed between TLRs and complement fragments and between TLRs and some inflammatory mediators. Our findings pointed at TLR2 and TLR4 over-expression at early stages of ERM formation, suggesting the participation of the local immune response in the severity of disease. These activations at the early-stage of ERM formation suggest a potential persistence of innate immune response in the early phases of fibrocellular membrane formation.

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.

Branch retinal artery occlusion caught in the act by an optical coherence tomography angiography image: case report.

BACKGROUND: Retinal artery occlusion is a vascular entity caused by the temporary blockage of retinal arterioles. CASE PRESENTATION: We present the case of a 57-year-old woman a partial visual loss in the right eye due to a cilioretinal artery occlusion. Ophthalmoscopy revealed a focal area of retinal whitening superior to the optic nerve in the right eye, while the left eye was within the limit. Retinal imaging, in particular optical coherence tomography angiography (OCTA), showed a capillary drop out of the superficial capillary plexus and the corresponding b-scan showed a round hyporeflective grey dot (optical empty) corresponding to the dark grey spot on the enface view at the level of the retinal whitening area. CONCLUSION: Although the images did not allow the differentiation between vasospasm or retinal emboli, the OCTA imaging might help to identify and to caught in the act the specific region causing the retinal impairment. Also, the possible formation of small microcavity should be considered in case with branch retinal artery occlusion. The use of this new imaging technology might help to evaluate the efficacy of the therapy in vivo.

Could Small Neurotoxins-Peptides be Expressed during SARS-CoV-2 Infection?

SARS-CoV-2 pathogenesis has been recently extended to human central nervous system (CNS), in addition to nasopharyngeal truck, eye, lung and gut. The recent literature highlights that some SARS-CoV-2 spike glycoprotein regions homologous to neurotoxin-like peptides might bind to human nicotinic Acetyl-Choline Receptors (nAChRs). Spike-nAChR interaction can probably cause dysregulation of CNS and cholinergic anti-inflammatory pathways and uncontrolled immune-response, both associated to a severe COVID-19 pathophysiology. Herein, we hypothesize that inside the Open Reading Frame (ORF) region of spike glycoprotein, the RNA polymerase can translate small neurotoxic peptides by means of a "jumping mechanism" already demonstrated in other coronaviruses. These small peptides can bind the snAChRs instead of Spike glycoproteins. A striking homology occurred between these small peptides observed by sequence retrieval and proteins alignment. Acting as nAChRs antagonists, these small peptides (conotoxins) could be the explanation for the extrapulmonary clinical manifestations (neurological, hemorrhagic and thrombotic expressions, the prolonged apnea, the cardiocirculatory collapse, the heart arrhythmias, the ventricular tachycardia, the body temperature alteration, the electrolyte K+ imbalance and finally the significant reduction of butyryl cholinesterase (BuChE) plasma levels, as observed in COVID-19 patients. Several factors might induce the expression of these small peptides, including microbiota. The main hypothesis regarding the presence of these small peptides opens a new scenario on the etiology of COVID-19 clinical symptoms observed so far, including the neurological manifestations.

Phacoemulsification and nucleic acid-enriched aerosol: considerations from an eye model of cataract simulation.

PURPOSE: The purpose of this study is to investigate whether phacoemulsification can generate aerosolized single-stranded RNA (ssRNA) and retain sequence integrity using an artificial eye model for experimental cataract surgery. METHODS: A simulation of cataract surgery was performed using an anterior chamber eye model filled with an ssRNA probe at different scalar dilutions (kanamycin positive control ssRNA). A plastic conical cage was built over the artificial eye surface of the mock-up. A total of 24 tests (twice reproduced) were performed, and five nitrocellulose strips were placed 15 cm from the artificial surface of the mock-up and used to collect aerosol particles, from each experiment. Phaco-activity was mimicked using a phacoemulsification equipped with a 2.75-mm tip, and strips were removed at the end of the procedure. RNA extraction, reverse transcription, and agarose gel electrophoresis were performed and compared. RESULTS: Strips collected aerosol droplets enriched with ssRNA, mainly at the higher concentrations tested, compared to related untouched standard solutions. Complementary DNA (cDNA) synthesis confirmed the presence of intact ssRNA fragments. As observed from densitometric analysis of resolved RNA in extracted samples and cDNA bands after retro-transcription, lower concentrations of ssRNA were also detected. CONCLUSIONS: As the main output of the study, the phaco-generated aerosol can deliver an intact ssRNA sequence. Since the aerosol can potentially reach the operator's face, any biological agent (virus/bacteria) potentially inside the anterior chamber of a patient undergoing cataract surgery, eventually escaping from biomolecular checks, can be potentially infective for operators. The data reported herein suggest that collective versus individual protective countermeasures should always be encouraged in ocular surgery and should not be restricted to coronavirus disease emergencies.

NGF in Inflammatory and Neurodegenerative Diseases of the Eye: New Findings Supporting Neuroprotection and Proper Tissue Remodeling in Vitreoretinal Disorders.

Nerve growth factor (NGF) plays a crucial role in retinal disorders, as suggested by in vitro/in vivo models. The major effect embraces the neuroprotective activity on retinal ganglion cells (RGCs) undergoing degeneration, as observed in experimental diabetic retinopathy, age-related and diabetic macular degeneration, and some vitreoretinal diseases. Focused experiments suggested that locally applied NGF (intravitreal delivery) not only allowed the counteraction of RGC degeneration but also provided data for a whole retina restoration. The currently available retinal microsurgery allows the collection of human aqueous and more interesting vitreous (vitreal reflux) humors. The recent biomolecular analysis highlights the possibility to identify disease-associated biomarkers and allow the monitoring of retinal impairments with sustain to the retinal imaging. Coupled to other soluble mediators, NGF has been quantified in aqueous (slightly expressed) from diabetic retinopathy-suffering patients (cataract surgery) and vitreal reflux (significantly impaired) of diabetic macular degeneration-suffering patients (intravitreal surgery). Although the reasons of these NGF impairments are not fully comprehended, some retinal cells (glial cells, bipolar neurons, and RGCs) have been recognized partially responsible for these local changes.Taken together, the recent progress in the ocular microsurgeries might be associated with sampling of small amount of ocular humors, allowing the collection of biochemical information about diseased retina and the monitoring of treatment. The chance to detect NGF and likewise other neuroprotective or pro-/anti-inflammatory factors in these fluids would open to the possibility to identify biomarkers of early diagnosis or monitoring of retinal disease evolution/therapy (precision medicine).

Osteopontin in vitreous and idiopathic epiretinal membranes.

PURPOSE: To investigate osteopontin (OPN) expression in vitreous and in related idiopathic epiretinal membranes (ERMs), with respect to VEGF-A, IL8, MIP1α, IL6, and IL33, and correlate OPN expression with disease staging. METHODS: Fifteen (15) vitreous and allied ERMs were collected at the time of therapeutic vitreoretinal surgery. Additional 5 vitreous and 10 ERMs (historical collection) were used. Biochemical and molecular analysis of OPN was performed in clear vitreous, vitreal pelleted cells, and ERMs. Double-immunofluorescence analysis (OPN - GFAP and OPN - αSMA) was performed on paraffin and whole-mounted ERMs. Vitreal OPN levels were correlated to those of VEGF-A, IL8, MIP1α, IL6, and IL33. RESULTS: High OPN levels were observed in vitreal samples, and OPN transcripts were amplified in vitreal cells and related ERMs. OPN immunoreactivity was found in ERMs, mainly in GFAP-bearing (Muller cells) and to a less extend in αSMA-expressing (myofibroblasts) cells. OPN levels were highest at early stages of ERM formation and positively correlated to VEGF-A and MIP1α. CONCLUSIONS: High OPN levels in vitreous, OPN transcripts in vitreal cells/ERMs, OPN immunoreactivity in activated Müller cells and contractile myofibroblasts, as well as the correlation with VEGF-A and MIP1α fulfill the potential involvement of OPN in both inflammation and tissue remodeling that takes part in vitreoretinal interface disorders. The highest OPN levels at early stages of ERM formation would prospect OPN as a potential biomarker for disease severity.

Short-term changes in posterior vitreous cortex following intravitreal ocriplasmin for symptomatic vitreomacular traction syndrome: a prospective study.

PURPOSE: To describe and analyze short-term posterior vitreous abnormalities following intravitreal ocriplasmin in eyes with symptomatic vitreomacular traction syndrome (VMT). METHODS: In this institutional, prospective and interventional study enrolled patients with symptomatic focal VMT syndrome treated with intravitreal ocriplasmin. In all cases, spectral-domain optical coherence tomography scans were quantitatively and qualitatively analyzed preoperatively and at 1 and 4 weeks postoperatively. RESULTS: Twenty-three patients, of which 5 were males and 18 females, with a mean age of 69.5 ± 8.2 years were included in this study. Postoperatively, VMT resolved in 11 of 23 eyes (47.8%). In 9 out of 11 cases (81.8%), VMT resolved by postoperative week 1, whether in the remaining 2 (18.2%) anatomical restoration, was diagnosed at postoperative week 4. At postoperative week 1, a foveolar detachment was detected in 9 out of 23 eyes (39.1%). The foveolar detachment resolved all but one eye by the end of postoperative week 4. At the end of the follow-up period, the presence of subretinal fluid was detected in 7 out of 9 eyes (77.8%), and it was significantly associated with a shrinkage of the posterior vitreous cortex (p < 0.006). At the end of the follow-up period, visual acuity was significantly higher in those eyes with VMT resolution (p < 0.001). CONCLUSION: Intravitreal ocriplasmin is effective for the treatment of patients with VMT. The postoperative presence of posterior hyaloid shrinkage may be associated with higher traction over the foveal area and the appearance of foveolar detachment.

Inflammatory mediators in the vitreal reflux of patients with diabetic macular edema.

PURPOSE: To quantify inflammatory, growth/angiogenic, and tissue remodeling mediators in vitreal reflux (VR) in patients with diabetic macular edema (DME), as collected at first and third intravitreal anti-vascular endothelial growth factor (anti-VEGF, ranibizumab) injection. METHODS: Thirty (30) consecutive patients (type-2 diabetes mellitus) with visual impairments due to DME and undergoing the first (untreated DME) or the third (treated DME) intravitreal injection of anti-VEGF were included in the study. At the time of surgery, patients were subjected to clinical assessment and spectral domain-optical coherence tomography (SD-OCT), including central retinal thickness (CRT), macular volume, and outer nuclear layer/retinal pigment epithelial (ONL/RPE) measurements. VR sampling was performed at the time of needle removal and subjected to customized protein-array, Western blotting (WB), Ella™ microfluidic, and/or enzyme-linked immunosorbent assay (ELISA) analysis. Biostrumental and biochemical data were collected just prior to the surgery and are representative of disease state. Clinical, biostrumental, and numerous biomarkers and cytokines were statistically compared. RESULTS: Decreased CRT values were detected in treated DME retinas, as compared to untreated ones (p ≤ 0.05). Differences in VEGF and other mediator expressions between treated and untreated DME were detected in VR samples. Particularly, osteopontin (p ≤ 0.05), interleukin 6 (IL6) (p ≤ 0.05), and VEGF (p ≤ 0.1) values were decreased after treatment. Significant changes were validated by WB, ELISA, and Ella™ analysis. CONCLUSION: Overall, the biostrumental and biochemical data suggest the presence of a specific pattern of inflammation in VR after treatment. The data would suggest the presence of other mechanisms and mediators, in addition to VEGF, accountable for DME progression.

CORRELATION BETWEEN OUTER RETINAL THICKENING AND RETINAL FUNCTION IMPAIRMENT IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANES.

PURPOSE: To examine the relationship between retinal layer thickness, retinal sensitivity, and visual function in patients with idiopathic epiretinal membrane using spectral domain optical coherence tomography automated segmentation algorithm. METHODS: Twenty-four eyes with epiretinal membrane and 12 control eyes were enrolled. Ophthalmic evaluations included best-corrected visual acuity, mean retinal sensitivity (MRS) of radial 10° and 4° areas tested with microperimetry, and measurements of 4 retinal layer thicknesses by means spectral domain optical coherence tomography. Relations between retinal layer thickness, MRS, and best-corrected visual acuity values were explored. RESULTS: Compared with controls, MRS (P < 0.001) and best-corrected visual acuity (P < 0.001) values were reduced. In the epiretinal membrane group, MRS of the central 4° values was associated with thickening of the outer nuclear layer (P < 0.05). Furthermore, a correlation was found between the inner nuclear layer thickening and the MRS of the central 4° limited to the inferior quadrant (P < 0.05). The decreased best-corrected visual acuity values were correlated with the thickening of three of four quadrant of the inner nuclear layer, inferior and temporal quadrants of the outer plexiform layer, and finally outer nuclear layer nasal quadrant. CONCLUSION: We found a meaningful correlation between MRS impairment of the central 4° and outer nuclear layer thickness and showed which intraretinal layers mainly contributes to visual acuity loss.

LONGITUDINAL MICROPERIMETRY EVALUATION AFTER INTRAVITREAL OCRIPLASMIN INJECTION FOR VITREOMACULAR TRACTION.

PURPOSE: To determine whether improvements in microperimetry testing are associated with anatomic resolution after ocriplasmin treatment in patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction and relatively preserved baseline best-corrected visual acuity (BCVA). METHODS: Patients with vitreomacular traction received a single 125-µg intravitreal ocriplasmin injection and were followed longitudinally for 6 months with optical coherence tomography, BCVA testing, and microperimetry. Visual function changes were compared between eyes with and without VMA resolution on optical coherence tomography. RESULTS: Eleven of 16 eyes (68.8%) achieved VMA resolution after treatment. Mean baseline BCVA was relatively good (79 ± 3 Early Treatment Diabetic Retinopathy Study letters; 20/52); no patients had a ≥2-line improvement in BCVA over the 6-month follow-up period. In the group with VMA resolution, mean retinal sensitivity significantly increased in the central 4° (15.2 ± 1.9 dB vs. 18.9 ± 0.7 dB, P < 0.001) when comparing baseline and final follow-up microperimetry testing. No change in mean retinal sensitivity was found in the group without VMA resolution. CONCLUSION: Microperimetry demonstrates a significant gain in retinal sensitivity, particularly in the central 4° area, in eyes with anatomic resolution after treatment of vitreomacular traction with intravitreal ocriplasmin injection, even when no significant gain in BCVA is seen.

LASER PROPHYLACTIC TREATMENT OF THE FELLOW EYE IN GIANT RETINAL TEARS: Long-Term Follow-up.

PURPOSE: To report the results of a retrospective study on prophylactic laser treatment versus observation of giant retinal tears (GRTs) fellow eyes. METHODS: One hundred and sixty consecutive charts of patients operated for GRT were included in this retroprospective study. Standard office visit included manifest and corrected refraction, intraocular pressure measurement, slit-lamp examination of the anterior and posterior segment with +90 diopter lens, and indirect ophthalmoscopy were performed at baseline and during follow-up period. RESULTS: Observation group included 62 and prophylactic laser treatment group 98 eyes. The incidence of retinal tears with localized preequatorial retinal detachment, GRTs with macula-ON retinal detachment, and GRTs with Macula-OFF retinal detachment were 3.2, 0, and 14.5%, respectively, during 43.5 ± 19.8 months of follow-up period in observation group and 11.2, 2, and 0%, respectively, in prophylactic laser treatment group during 37.2 ± 16.3 months of follow-up period. CONCLUSION: Prophylactic laser treatment of GRTs fellow eyes decreased the incidence of GRTs and limited the consequences of newly developed tears, lowering the occurrence of a macula-off retinal detachment with a consequent better final visual outcome respect to observation group.

ADJUSTABLE MACULAR BUCKLING FOR FULL-THICKNESS MACULAR HOLE WITH FOVEOSCHISIS IN HIGHLY MYOPIC EYES: Long-Term Anatomical and Functional Results.

PURPOSE: To assess functional and structural outcome after adjustable macular buckling for the treatment of foveoschisis (FS), associated with full-thickness macular hole (FTMH) in highly myopic eyes. METHODS: Eighteen consecutive patients who underwent adjustable macular buckling for FS associated with FTMH were included in this prospective study. Three cases were not included in the analysis due to short follow-up period (less than 3 months). Outcome measures included anatomical success rate with FS resolution and FTMH closure, best-corrected visual acuity, mean retinal sensitivity, central retinal thickness, and fixation site and stability. RESULTS: Foveoschisis resolution and FTMH closure were observed in all cases between 1 month to 3 months after surgery. At 24 months of follow-up visit visual acuity improved in 13/15 eyes (86.7%) and remained stable in 2 (13.3%). Mean retinal sensitivity showed significant improvement from baseline 5.69 ± 3.52 dB to final 8.35 ± 3.86 dB; P < 0.001. Fixation stability inside central 4° improved from baseline 58.5 ± 17.8% to final 73.7 ± 23.0%; P = 0.009. Central retinal thickness did not change significantly throughout follow-up. No FTMH or FS recurrence occurred and no surgical complications arose. CONCLUSION: Adjustable macular buckling exoplant may represent an effective surgical option for the treatment of FS associated with FTMH in highly myopic eyes. Adjustable macular buckling showed high closure rate and virtually no tendency to recur. Functional results and safety are also interesting because vision improved and retinal thickness did not reduce significantly at 24 months of follow-up.

Intravitreal ranibizumab for predominantly hemorrhagic choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the effects of intravitreal ranibizumab monotherapy on predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. MATERIALS AND METHODS: Twenty-two consecutive eyes with hemorrhagic neovascularization were treated with 3 monthly intravitreal ranibizumab injections. Additional injections were administered according to retreatment criteria during 12 months of follow-up. RESULTS: A mean of 6.64 ± 1.36 injections was administered. Overall, the mean visual acuity increased from 10.90 ± 6.02 to 12.81 ± 8.34 ETDRS letters (p > 0.05) at 12 months. The 'early treatment group' gained a mean of 2.83 ± 2.24 ETDRS letters (p < 0.05), while the 'late treatment group' gained a mean of 0.30 ± 1.25 ETDRS letters (p > 0.05) with significant differences between the groups (p < 0.05). A progressive resolution of macular bleeding was registered in 20 patients (mean time: 5.3 ± 1.6 months). CONCLUSIONS: Ranibizumab injections can be considered a beneficial approach for the management of predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. Furthermore, the time interval between hemorrhage and the first injection seems to be an important predicting factor of final visual acuity.

Influence of macular choroidal thickness on visual function in highly myopic eyes.

PURPOSE: To explore the retinal and choroidal thicknesses (RT, CT), as measured using enhanced depth imaging (EDI) optical coherence tomography (OCT, Spectralis) in highly myopic eyes and its relationship with visual function. MATERIALS AND METHODS: Prospective, case-control, noninterventional clinical study. CT was measured by EDI-OCT in highly myopic eyes (≥6 dpt) without any macular diseases and age-matched control eyes. A complete ophthalmological examination, visual acuity assessment and MP1 microperimetry were obtained. RESULTS: 38 myopic (15 M/23 F, mean age 51 ± 8.9 years) and 21 control eyes (5 M/16 F, mean age 50 ± 5.4 years) were included. The myopic mean refractive error was -13.3 ± 4.9 dpt and axial length 29.2 ± 2.2 mm. The mean best-corrected visual acuity (BCVA) was lower in highly myopic than in control eyes (77.3 ± 9.25 vs. 84.8 ± 0.6 letters, p = 0.0001, respectively) as was the mean retinal sensitivity (MRS; 16.32 ± 2.6 vs. 19.9 ± 0.2 dB, p < 0.0001). While RT was similar between groups (291.5 ± 24.2 vs. 283.6 ± 13.9 µm, p = 0.06, respectively), subfoveal CT was thinner in highly myopic compared to control eyes (114.3 ± 78.5 vs. 272.6 ± 110.2 µm, p < 0.0001). A significant relationship was found between subfoveal CT and MRS (R(2) = 0.22; p = 0.003) and BCVA (R(2) = 0.13; p = 0.027). CONCLUSIONS: Macular function is reduced in highly myopic eyes without any visible macular diseases compared to controls, and a significant proportion of the macular function variability seems to be related to a reduced CT.

Choroidal thickness changes with photodynamic therapy for a diffuse choroidal hemangioma in Sturge­Weber syndrome.

The aim of this study was to evaluate the choroidal thickness (CT) changes associated with visual function following photodynamic therapy (PDT) for a diffuse choroidal hemangioma in Sturge­Weber syndrome. We report a case of Sturge­Weber syndrome and symptomatic serous retinal detachment (SRD) with diffuse choroidal hemangioma treated with PDT. Visual acuity (VA), macular sensitivity measured by means of MP1 microperimeter (Nidek Technologies, Padova, Italy), retinal and CT, measured by means of enhanced depth optical coherence tomography (EDI­OCT, Spectralis, Heidelberg Engineering, Heidelberg, Germany) were analyzed at baseline, 3 and 12 months follow-up.After the PDT VA and macular sensitivity improved.The OCT examination showed the resolution of SRD. The choroid was measured after PDT using EDI­OCT. At baseline, the subfoveal CT showed a progressive thickness reduction from 251 to 83 lm during follow-up. To our knowledge, this is the first report of CT changes after PDT for a diffuse choroidal hemangioma in Sturge­Weber syndrome in a longterm follow-up. The CT measurement represents a potential parameter to better follow choroidal hemangiomas and their response to treatment. However,the long-term choroidal changes should be carefully taken into account.

Single-session photodynamic therapy combined with intravitreal ranibizumab for neovascular age-related macular degeneration: a comprehensive functional retinal assessment.

PURPOSE: To explore functional retinal changes in neovascular AMD patients (nAMD) treated with ranibizumab 0.5 mg combined with photodynamic therapy (PDT) 3 days after the first injection in the long term. METHODS: Patients with no prior treatment for nAMD were treated with 3 injections of ranibizumab 0.5 mg 1 month apart and a single session of standard PDT 3 days after the first injection. Best-corrected visual acuity and time-domain OCT at baseline and every 28 ± 2 days were performed; microperimetry at 3, 6, and 12 months and multifocal electroretinogramm (mfERG) at 3 and 12 months were repeated. Fluorescein angiography and vision-related quality-of-life questionnaire were performed at baseline and 12 months. RESULTS: 12/15 nAMD patients completed the 12 months study and received an average of 3.4 ± 0.7 injections. Mean VA changed from 54.67 ± 15.72 to 59.0 ± 24.77 letters (p = 0.371), while mean retinal sensitivity from 5.5 ± 4.8 to 6.6 ± 6.0 dB (p = 0.216). MfERG N1-P1 response amplitude densities (RADs) were significantly different from baseline (p < 0.01) in the central 0°-2.5°, whereas in the peripheral retinal areas (2.5°-20°), not significant (p > 0.01) changes in N1-P1 RADs were detected. The "general vision" VFQ-25 subscale showed a statistically significant improvement at 3 and 12 months. CONCLUSIONS: Ranibizumab 0.5 mg combined with standard PDT 3 days after the first injection determines an improvement of mfERG values in the retinal central area in nAMD patients in long-term follow-up.

Functional retinal impairment in type 1 diabetic patients without any signs of retinopathy.

PURPOSE: To investigate functional and morphological retinal changes in the long-term follow-up in subjects with type 1 diabetes mellitus (DM1) without any signs of retinal vasculopathy. METHODS: Functional testing included Humphrey Matrix perimetry (30-2 threshold program) and white-on-white Humphrey perimetry (HFA, 30-2 SITA standard), while retinal nerve fibre layer (RNFL) thickness was measured by scanning laser polarimetry with variable corneal birefringence compensator. RESULTS: Data from 20 eyes of 20 subjects with DM1 were analysed. No changes of HFA mean deviation (MD: -2.20 ± 3.44 vs. -1.63 ± 2.47; p = 0.14) and pattern standard deviation (PSD: 2.50 ± 1.71 vs. 2.28 ± 1.36; p = 0.31), and Matrix MD (-1.06 ± 3.62 vs. -1.24 ± 2.99; p = 0.65) were found after 5 years. A significant change was found for Matrix PSD between baseline and the end of follow-up (2.76 ± 0.59 vs. 3.1 ± 0.68; p = 0.0078). RNFL parameters were not changed. A significant relationship was found between HbA1c levels and changes from baseline of Matrix PSD (R(2) 0.29, p = 0.02). CONCLUSIONS: Progressive retinal functional impairment could be detected in DM1 subjects by frequency doubling perimetry before the onset of any overt retinal vasculopathy and functional impairment seems to be significantly related to glycaemic control.

Biomarker Signature in Aqueous Humor Mirrors Lens Epithelial Cell Activation: New Biomolecular Aspects from Cataractogenic Myopia.

Inflammatory, vasculogenic, and profibrogenic factors have been previously reported in vitreous (VH) and aqueous (AH) humors in myopic patients who underwent cataract surgery. In light of this, we selected some mediators for AH and anterior-capsule-bearing lens epithelial cell (AC/LEC) analysis, and AH expression was correlated with LEC activation (epithelial-mesenchymal transition and EMT differentiation) and axial length (AL) elongation. In this study, AH (97; 41M/56F) and AC/LEC samples (78; 35M/43F) were collected from 102 patients who underwent surgery, and biosamples were grouped according to AL elongation. Biomolecular analyses were carried out for AH and LECs, while microscopical analyses were restricted to whole flattened AC/LECs. The results showed increased levels of interleukin (IL)-6, IL-8, and angiopoietin-2 (ANG)-2 and decreased levels of vascular endothelium growth factor (VEGF)-A were detected in AH depending on AL elongation. LECs showed EMT differentiation as confirmed by the expression of smooth muscle actin (α-SMA) and transforming growth factor (TGF)-ßR1/TGFß isoforms. A differential expression of IL-6R/IL-6, IL-8R/IL-8, and VEGF-R1/VEGF was observed in the LECs, and this expression correlated with AL elongation. The higher VEGF-A and lower VEGF-D transcript expressions were detected in highly myopic LECs, while no significant changes were monitored for VEGF-R transcripts. In conclusion, these findings provide a strong link between the AH protein signature and the EMT phenotype. Furthermore, the low VEGF-A/ANG-2 and the high VEGF-A/VEGF-D ratios in myopic AH might suggest a specific inflammatory and profibrogenic pattern in high myopia. The highly myopic AH profile might be a potential candidate for rating anterior chamber inflammation and predicting retinal distress at the time of cataract surgery.