Severity of Disorganization of Retinal Layers and Visual Function Impairment in Diabetic Retinopathy.

PURPOSE: To evaluate best-corrected visual acuity (BCVA), retina sensitivity (RS), and fixation impairment by microperimetry (MP) due to the presence and severity of disorganization of retinal inner and outer layers (DRIL/DROL) and ischemia in OCT/OCT angiography (OCTA) in diabetic retinopathy (DR). DESIGN: Retrospective case-control study. SUBJECTS: Seventy-six eyes (65 patients) with DR were analyzed. Major exclusion criteria were: center-involving diabetic macular edema (DME), significant media opacity, nondiabetic macular pathology, and active proliferative DR. Patients with DRIL and DROL within central 3 mm were enrolled as cases. Patients with DR and no retina disorganization were considered as controls. METHODS: A detailed grading of MP and OCT/OCTA images using Image J software, and specific Image Manipulation Program was applied to colocalize the presence of retina disorganization and RS. Best-corrected visual acuity and RS were correlated with the disorganization of retina layers' characteristics and grading (grade 1-DRIL; grade 2-DROL; grade 3-DROL plus, with involvement of the ellipsoid zone). The same procedure of colocalization was applied to the vascular layers on OCTA using MATLAB. MAIN OUTCOME MEASURES: Correlation between BCVA and MP parameters with disorganization of retina layers grading and OCTA parameters. RESULTS: Best-corrected visual acuity, mean RS within 1 mm and central 3 mm (overall RS [oRS]), perfusion density, vessel density, and geometric perfusion deficit in intermediate and deep capillary plexuses were lower in cases versus controls (P < 0.001). Mean RS within 1 mm (21.4 decibels [dB] ± 2.4 vs. 13.8 dB ± 5.4, P = 0.002), oRS (22.0 dB ± 2.1 vs. 14.4 dB ± 4.6, P < 0.001), and BCVA (76.1 ± 7.4 vs. 61.2 ± 20.4 ETDRS letters; P = 0.02), had a significant decrease from grade 1 to grade 3 retina disorganization. Choriocapillaris flow voids (CC-FVs) increased from grade 1 to grade 3 (DROL plus) (P = 0.004). Overall retina sensitivity and CC-FV were identified as significant predictors of retina disorganization grade with an adjusted coefficient of determination, R2 = 0.45. Cases had more dense scotomas (P = 0.03) than controls with a positive correlation between the worsening of fixation stability and the severity of DRIL/DROL (P = 0.04). CONCLUSIONS: Microperimetry and BCVA documented a reduction in visual function in patients with DR and disorganization of retina layers at different grades, with greater functional impairment when outer retina layers and photoreceptors are involved. The severity of retina disorganization and the presence of ischemia could serve as a potential biomarker of functional impairment. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Epidemiology of geographic atrophy and its precursor features of intermediate age-related macular degeneration.

Globally age-related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers. The incidence and prevalence of GA varies across different geographic regions, with the highest rates in those of European ancestry. Although heterogeneity in definitions of GA and reporting strategy can explain some of the discrepancies, the data overall are consistent in showing a lower prevalence in other ethnicities such as those of Asian heritage. This is at present unexplained but thought to be due to the existence of protective factors such as differences in eye pigmentation, diet, environmental exposures and genetic variability. This review covers key aspects of the prevalence and incidence of the ocular precursor features of GA (large drusen, pigmentary abnormalities and reticular pseudo-drusen), the late stage of GA and factors that have been known to be associated with modifying risk including systemic, demographic, environment, genetic and ocular. Understanding the global epidemiology scenario is crucial for the prevention of and management of patients with GA.

Treat and extend versus fixed regimen in neovascular age related macular degeneration: A systematic review and meta-analysis.

PURPOSE: To compare efficacy of treat and extend (T&E) versus fixed regimen treatment protocols in neovascular age-related macular degeneration (nAMD). METHODS: Randomized clinical trials (RCTs) comparing T&E versus fixed regimen protocols for nAMD were systematically searched. Primary outcome was to compare the mean best corrected visual acuity (BCVA) change in T&E regimen versus fixed regimen. Secondary outcomes were change in the mean optical coherence tomography (OCT) central retinal thickness (CRT) and mean number of injections. Standardized mean difference (SMD) along with 95% confidence intervals (CIs) were calculated. Random-effect models were used for meta-analyses. RESULTS: Four RCTs were included, with a total of 649 and 621 eyes in the T&E and fixed regimen cohort at 12 months, and 267 and 249 eyes at 24 months. Pooled analysis of mean BCVA change included all four RCTs at 12 months and two RCTs at 24 months, showing no difference between the two groups (12-month: SMD = 0.08, 95% CI: -0.20 to 0.35, p = 0.55; 24-month: SMD = 0.04, 95% CI: -0.13 to 0.21, p = 0.64). Pooled analysis of OCT CRT change at 12 months included three studies, showing no difference between the two groups (SMD = 0.03, 95% CI: -0.46 to 0.51, p = 0.91). Pooled analysis of mean injection number included all four RCTs at 12 months and two RCTs at 24 months, showing significant difference between the two groups (12-month: SMD = -1.11, 95% CI: -1.67 to -0.56, p < 0.001; 24-month: SMD = -1.34, 95% CI: -1.54 to -1.15, p < 0.001). CONCLUSION: A T&E regimen proved as effective as a fixed dosage regimen throughout a 24-month follow-up and with a lower number of injections.

Choroidal Structure after Half-Dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

The study aims to analyze the changes produced by half-dose photodynamic therapy (HD-PDT) in the choroid of eyes with chronic central serous chorioretinopathy (CSC) applying the binarization method to spectral domain optical coherence tomography (SDOCT) and OCT Angiography (OCTA) images. SDOCT and OCTA were performed before, one hour, one week, and one month after HD-PDT. Binarization with a modified Niblack method and analysis by ImageJ were applied. An average ratio between luminal part and total structure was calculated. Twenty-two eyes of 21 patients (20 male and 1 female; mean age 54.8 years) were enrolled. A statistically significant reduction of the central choroidal thickness was observed one week (from 407 µm to 362 µm, p = 0.034) and one month (from 407 µm to 341.5 µm, p = 0.0004) after HD-PDT. The baseline average ratio between luminal part and total structure was 33.4% in SDOCT, and 61.1% in OCTA. These values were 35.3% and 61% one hour, 33.9% and 60.4% one week, and 34.5% and 60.6% one month after HD-PDT, respectively. Overall, PDT seems to produce short-term changes on the luminal component of both choriocapillaris and choroid, which return to baseline status after one month from treatment. However, choroid stays significantly thinner after one month, with both luminal and interstitial components significantly reduced.

Clinical Course of Autosomal Recessive Bestrophinopathy Complicated by Choroidal Neovascularization.

The authors report the clinical course of two cases of autosomal recessive bestrophinopathy (ARB) complicated by choroidal neovascularization (CNV). One patient presenting with a novel BEST1 mutation (c.658 C>T, p.Gln220*) underwent anti-vascular endothelial growth factor therapy. Response to treatment was documented on optical coherence tomography angiography (OCTA). Despite initial response to treatment, recurrent CNV exudation with progressive subretinal fibrosis was observed. In the second patient, the CNV was not treated and spontaneous regression was observed. This report indicates that the clinical course of CNV in ARB may vary considerably, ranging from spontaneous regression to progressive subretinal fibrosis despite intervention. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:888-892.].

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

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

Short-Term Choriocapillaris Changes in Patients with Central Serous Chorioretinopathy after Half-Dose Photodynamic Therapy.

BACKGROUND: Although photodynamic therapy (PDT) has become the standard treatment for central serous chorioretinopathy (CSC), its mechanism of action remains unclear. It is assumed that PDT induces short-term choriocapillaris (CC) occlusion and long-term choroidal vascular remodeling. In this paper, we describe the short-term CC changes induced by Half-Dose PDT (HD-PDT) in chronic CSC using optical coherence tomography-angiography (OCTA). METHODS: This is a prospective interventional case series. Chronic CSC eyes underwent Spectral-Domain OCT, Fundus Autofluorescence, FA, ICGA (Heidelberg Spectralis, Heidelberg, Germany) and OCTA (RTVue XR Avanti with AngioVue; Optovue Inc., Fremont, CA, USA) before HD-PDT, with follow-up after one hour, one week, and one month. Vascular changes after PDT were analyzed within the CC layer. The CC vessel density was defined as the percentage of an area occupied by flow pixels, using Image J software to obtain measurements by applying a grey level threshold. All pixels with a grey level above the threshold were considered as indicators of blood flow. RESULTS: 20 eyes of 19 patients were included. At baseline the mean CC vessel density was 94.87 ± 2.32%. It significantly differed from the density at 1 week and 1 month (92.79 ± 3.16% and 95.55 ± 2.05%, p < 0.001, respectively), but not with values at 1 h (94.8 ± 2.28%, p = 0.516). CONCLUSIONS: CC vessel density was significantly reduced at 1 week as compared with baseline, suggesting a possible short-term effect of PDT on CC perfusion. After 1 month however, the CC vessel density was even higher than the baseline, probably due to a CC recovery. OCTA seems to be useful in the visualization of CC vessels and in confirming the mechanism of action of PDT treatment in eyes with chronic CSC.

Vitreous Substitutes: Old and New Materials in Vitreoretinal Surgery.

Recent developments in vitreoretinal surgery have increased the need for suitable vitreous substitutes. A successful substitute should maintain all the physical and biochemical properties of the original vitreous, be easy to manipulate, and be long lasting. Substitutes can be gaseous or liquid, both of which have associated advantages and disadvantages related to their physical properties and use. Furthermore, new surgical techniques with smaller vitreoretinal instruments have driven the use of more viscous substitutes. In this review, we analyze and discuss the most frequently used vitreous substitutes and look ahead to future alternatives. We classify these compounds based on their composition and structure, discuss their clinical use with respect to their associated advantages and disadvantages, and analyze how new vitreoretinal surgical techniques have modified their use.

Indocyanine Green Angiography and Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration.

Purpose: To compare the capability of indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in detecting choroidal neovascularization (CNV). Methods: In this prospective study, patients with CNV detected with fluorescein angiography (FA) underwent ICGA and OCTA, spectral domain OCT (SD-OCT), and infrared or fundus color photographs. CNV lesions were outlined on ICGA and OCTA images, and the composition and size of the CNV was documented. Results: One hundred eighty-two eyes were included. With ICGA, well-defined lesions were observed in 37.9%, partly defined in 44.5%, and undefined in 17% of eyes. On OCTA, well-defined, partly defined, and undefined vessels were observed in 53.8%, 27.5%, and 18.7% of eyes, respectively. There was a good correlation between CNV size measured with the two instruments (r = 0.84). However, OCTA underestimated CNV area by about 4.5% (slope coefficient with linear regression: 0.55, 95% confidence interval [CI]: 0.46 to 0.65; intercept: 0.27, 95% CI: -0.2 to 0.56). On ICGA, CNV composition was capillary in 28%, mature in 14.3%, and mixed (capillary and major neovascular complex) in 57.7% of eyes. Similarly, OCTA revealed capillary, mature, and mixed CNV in 28.9%, 15.9%, and 55.5% of eyes, respectively. Conclusions: OCTA provides the clinician the ability to perform precise structural and vascular assessment of CNV noninvasively. Our study is, to our knowledge, the largest OCTA analysis to date of CNV secondary to neovascular AMD analyzed simultaneously by ICGA and OCTA.

Macular Pigment Density and Quantitative Fundus Autofluorescence in Young Healthy Subjects.

Purpose: To measure macular pigment (MP) and find possible correlation between heterochromatic flicker photometry (HFP) and quantitative autofluorescence (qAF) in young healthy subjects. Methods: We enrolled 80 eyes of 40 young healthy subjects. Macular pigment optical density (MPOD) was automatically calculated with a macular pigment screener (MPS; MPODHFP). We calculated qAF comparing gray levels (GL) of qAF images with GL of internal reference of a confocal scanning laser ophthalmoscopy. A raster of concentric rings was used to automatically calculate foveal qAF (qAFF) values (0°-1.2°); inner ring (1.3°-4.3°; qAF3); middle ring (4.5°-7°; qAF6); and outer ring (7.2°-9.7°; qAF8). The test-retest coefficient of repeatability was calculated with Bland-Altman method. The between-eyes coefficient of agreement and correlation between the two techniques were calculated. Finally, an estimation of MPOD from qAF was performed (MPOD-AF), to find possible direct correlations with MPODHFP obtained with the MPS II. Results: Paired data sets of repeated measurements were not statistically different for MPS II (P = 0.66); log qAFF (P = 0.95); log qAF3 (P = 0.48); log qAF6 (P = 0.4); and log qAF8 (P = 0.56). Stepwise regression analysis showed negative correlation between MPS II and log qAFF values (R2 = 0.35) with Spearman coefficient (ρ) of -0.60 (P < 0.01) and log qAF3 (R2 = 0.18; ρ = -0.38.; P < 0.01). No correlation was found between MPS II and log qAF6 (ρ = 0.01, P = 0.93), neither with log qAF8 (ρ = -0.05, P = 0.66). Conclusions: In young healthy subjects, a negative correlation between qAF values and MPODHFP was found in the central degrees. However, qAF and HFP do not seem to be interchangeable: they represent two opposite ways of estimating MP.

Changing trends in corneal graft surgery: a ten-year review.

AIM: To review indications and corneal tissue use for penetrating and lamellar surgery between 2002 and 2011. METHODS: The surgical reports of corneal grafts performed during 2002-2011, using tissues supplied by the Eye Bank of Piedmont (Italy), were reviewed retrospectively. Patient demographic data, date of intervention, indication for surgery, and surgical technique used were recorded. Surgical techniques included penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK). The χ (2) test was used to compare the distribution of indications and types of surgical technique used, for corneal grafts done during 2002-2006 versus those done during 2007-2011. RESULTS: The number of corneal grafts increased by 30.7% from 2002-2006 to 2007-2011 (from 1567 to 2048). Comparing the two periods, both main indications and surgical techniques changed significantly. In 2007-2011, the proportion of interventions for aphakic/pseudophakic bullous keratopathy (from 16.8% to 21.3%), graft failure (from 16.4% to 19.1%) and Fuchs endothelial dystrophy (from 12.8% to 16.7%) all increased significantly (P<0.05), while those for keratoconus decreased significantly (from 35.6% to 27.3%; P<0.001). In 2007-2011, the proportion of PK decreased significantly (from 92.4% to 57.2%; P<0.001) while that of EK and DALK went from 0.4% to 30.2% (P<0.001) and from 7.2% to 12.6% (P<0.001) respectively. CONCLUSION: During 2002-2011 the number of interventions increased significantly for corneal endothelial diseases and graft failure. The growing demand for interventions for these diseases corresponded to the widespread adoption of EK techniques. The use of DALK also increased, but more moderately than EK procedures.

Treatment for neovascular age related macular degeneration: The state of the art.

With the introduction in the clinical practice of drugs inhibiting vascular endothelial growth factor (VEGF) the visual outcomes of patients with neovascular age related macular degeneration (AMD) dramatically improved. Since 2006 repeated intravitreal injections of anti-VEGF became the standard of care for the treatment of neovascular AMD. This review provides an overview of available data form clinical trials supporting the use of anti-VEGF molecules for the treatment of this condition. Several questions remain open, in particular the regimen of treatment, the frequency of injection, the safety of the different drugs, and the poor response to the treatment in some cases. Therefore, new agents and alternative delivery are currently under evaluation.

Evaluation of Composite Adaptation to Pulpal Chamber Floor Using Optical Coherence Tomography.

INTRODUCTION: A coronal seal is fundamental for a positive outcome to endodontic therapy. In this in vitro study, we evaluated the adaptation of composite resins in postendodontic restorations using optical coherence tomographic (OCT) imaging. Our null hypothesis was that there would be no difference in marginal adaptation to the pulp chamber floor between resin composites of different viscosities. METHODS: Thirty intact upper molars extracted for periodontal reasons were selected, endodontically treated, and filled with gutta-percha. The excess gutta-percha was entirely removed from the pulp chamber floor, and teeth were randomly divided into 3 groups (n = 10) according to the material used for the restoration: group 1: 0.5-mm horizontal layer of flowable composite followed by nanohybrid composite, group 2: bulk layering of bulk fill flowable composite; and group 3: oblique layering of nanohybrid composite. The degree of adaptation to the cavity floor was assessed using OCT imaging, and images were analyzed with the software program ImageJ (National Institutes of Health, Bethesda, MD) to assess the marginal gap between the composite and the pulp chamber floor. Collected data were statistically analyzed using analysis of variance testing, and statistical significance was set at P < .05. RESULTS: Flowable composites showed significantly better adaptation than traditional packable nanohybrid composites (P < .05). All significant differences were found between groups 1 and 2. CONCLUSIONS: Within the limitations of this OCT imaging-based in vitro study, it was concluded that the flowable composite (flow + nanofilled; flow bulk fill composite) adapted better to the pulp chamber floor than the packable nanohybrid composite resin. Further studies are necessary to confirm these results.

Correlation between fundus autofluorescence and central visual function in chronic central serous chorioretinopathy.

PURPOSE: To find possible correlations between the morphologic macular changes revealed by fundus autofluorescence (FAF) and the functional parameters such as visual acuity and retinal sensitivity in patients with chronic central serous chorioretinopathy (CSC). DESIGN: Prospective, cross-sectional study. METHODS: Forty-six eyes (39 consecutive patients) with chronic CSC were studied with FAF and microperimetry (MP). Retinal sensitivity value maps were exactly superimposed over FAF images. The following microperimetric parameters were applied: central 10-degree visual field, 4-2-1 strategy, 61 stimulation spots, white monochromatic background, stimulation time 200 ms, stimulation spot size Goldmann III. A possible relationship between MP and FAF was investigated. RESULTS: Mean best-corrected visual acuity (BCVA) was 20/32 (median 20/25, range 20/20-20/200). BCVA was significantly correlated with FAF findings (Mann-Whitney test; P < .0001). A positive concordance between FAF and MP evaluation was also found (total concordance of 0.720 with a kappa of Cohen of 0.456). The hypo-autofluorescent areas showed decreased retinal sensitivity, while adjacent areas of increased FAF could be associated to both normal and decreased retinal sensitivity. Absolute scotoma, defined as 0 dB retinal sensitivity, corresponded with absence of autofluorescence. CONCLUSIONS: Altered FAF in chronic CSC patients has a functional correlation quantified by microperimetry. This study confirms the impact of FAF changes on retinal sensitivity and their value to reflect the functional impairment in chronic CSC.

Half-fluence versus half-dose photodynamic therapy in chronic central serous chorioretinopathy.

PURPOSE: To compare the efficacy and safety of half-fluence vs half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSC). DESIGN: Multicenter retrospective comparison study. METHODS: Retrospective review of 56 patients affected by chronic CSC, including 28 patients (31 eyes) who received half-fluence PDT and 28 patients (29 eyes) who received half-dose PDT. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and resolution of subretinal fluid on optical coherence tomography at 1 and 12 months were assessed. RESULTS: The mean logMAR BCVA improved significantly (P < .001), both in the half-fluence group (from 0.187 [± 0.187] to 0.083 [± 0.164]) and in the half-dose group (from 0.126 [± 0.091] to 0.068 [± 0.091]), at 12 months, without significant difference between the 2 groups. At 1 month a complete resolution of subretinal fluid was observed in 19 half-fluence-treated eyes (61.3%) and in 25 half-dose-treated eyes (86.2%) (P = .04). At 12 months, a complete resolution of subretinal fluid was achieved in 26 half-fluence-treated eyes (83.9%) and 29 half-dose-treated eyes (100%) (P = .0529). Nine eyes (29%) in the half-fluence group and 5 eyes (17.2%) in the half-dose group had at least 1 recurrence of subretinal fluid during the follow-up. Overall there were 15 and 5 recurrences in the half-fluence PDT and half-dose PDT groups, respectively (P = .07). In no eye of either groups was atrophy of the retinal pigment epithelium observed in the area of treatment. CONCLUSION: Half-dose PDT induced a more rapid reabsorption of the fluid, a more lasting effect, and equal safety with respect to half-fluence PDT.

Timogel® vs timolol 0.5% ophthalmic solution: efficacy, safety, and acceptance.

PURPOSE: To evaluate the efficacy, safety, and tolerability of Timogel® preservative-free once daily compared to timolol 0.5% ophthalmic solution bid in patients with ocular hypertension (OHT) and patients with primary open-angle glaucoma (POAG). METHODS: A total of 75 patients with OHT and patients with POAG treated with timolol 0.5% bid with intraocular pressure (IOP) ≤ 21 mmHg were enrolled. They underwent complete ophthalmologic examination, IOP measurements (at trough and daytime curve), evaluation of side effects, Schirmer test, break-up time [BUT], blood pressure, heart rate, ocular diastolic perfusion pressure measurements, and acceptance (Comparison of Ophthalmic Medications for Tolerability). Patients switched to Timogel® and were re-evaluated 3 months later. The analysis of variance and the Pearson Chi2 tests were used to test differences between the treatments. RESULTS: Intraocular pressure reduction at trough was 23.6% with timolol 0.5% and 22.3% with Timogel®. No statistical differences were observed in IOP values at trough and in the daytime curve between the 2 treatments. Local and systemic side effects were less frequent with Timogel® (hazard ratio: p<0.05). Patients demonstrated a significant improvement of Schirmer test and BUT (p<0.05) and a reduction of dryness and foreign body sensation (42.6% vs 15.4%; p<0.01) after switching to Timogel®. Mild and short-lasting blurred vision after Timogel® instillation occurred in about 18.5% of patients. A total of 82% of patients were satisfied or very satisfied with Timogel® vs 61% with previous treatment (p<0.01). CONCLUSIONS: Timogel® preservative-free dosed once every morning has a 24-hour hypotensive effect with a better safety profile than timolol 0.5% bid and it is well-accepted by patients. The once-daily dosing improved acceptance and compliance.