CONVENTIONAL INTERNAL LIMITING MEMBRANE PEELING VERSUS INVERTED FLAP FOR SMALL-TO-MEDIUM IDIOPATHIC MACULAR HOLE: A Randomized Trial.

PURPOSE: To compare conventional internal limiting membrane (ILM) peeling versus inverted flap technique in small-to-medium idiopathic macular hole. METHODS: Eyes with ≤400 µ m idiopathic macular holes were randomized into the conventional ILM peeling group (25 eyes) and inverted flap group (25 eyes). A 12-month follow-up was considered. Macular sensitivity (MS) change detected with MP-1 microperimetry was the primary outcome. Secondary outcomes included best-corrected visual acuity change, closure rate, anatomical findings on optical coherence tomography such as U-shape foveal contour, restoration of external limiting membrane, and ellipsoid zone. RESULTS: In both groups, MS improved throughout the follow-up. Final MS was greater in the conventional ILM peeling group compared with the inverted flap group, being 16.6 ± 2.3 dB versus 14.9 ± 2.9 dB, respectively ( P = 0.026). In both groups best-corrected visual acuity improved throughout the follow-up, with a final best-corrected visual acuity of 0.19 ± 0.14 logMar (20/31 Snellen) in the conventional ILM group and 0.22 ± 0.11 logMar (20/33 Snellen) in the inverted flap group ( P = 0.398). Anatomical hole closure was achieved in all cases. No difference in optical coherence tomography findings was shown between the two groups. CONCLUSION: A better final MS was found in eyes undergoing conventional ILM peeling. Inverted flap technique has disadvantages compared with conventional peeling for the treatment of small-to-medium idiopathic macular holes.

Early OCTA Changes of Type 3 Macular Neovascularization Following Brolucizumab Intravitreal Injections.

BACKGROUND AND OBJECTIVES: Brolucizumab is a novel anti-vascular endothelial growth factor (VEGF), whose efficacy has been shown in the Hawk and Harrier phase 3 clinical studies. The goal of the present case series is to report initial results of brolucizumab intravitreal injections (IVI) on type 3 neovascularization in neovascular age-related macular degeneration (nAMD), evaluated by optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: This is a bicentric retrospective case series. Patients with newly diagnosed type 3 MNV treated with brolucizumab IVI and at least 6 months follow-up were enrolled. OCTA en face images and B-scans were analyzed for lesions at baseline, 1 month, 3 months, and 6 months. Whenever detectable, lesion area on outer retina and choriocapillaris layers was measured. RESULTS: Twelve eyes of 12 patients were included into the study. The most consistent OCTA sign at baseline was the presence of a vascular tuft in the outer retina (100%). The highest response was achieved at 3 months, with statistically significant decrease in lesion detection in the outer retina, in the choriocapillaris, and outer retinal lesion size. At 6 months, 58% of outer retinal lesions had disappeared. CONCLUSIONS: Brolucizumab IVI shows a good short-term efficacy for the treatment of type 3 neovascularizations. Further studies with greater number of patients and longer follow-up are warranted to confirm these findings.

Polypoidal choroidal vasculopathy in pachychoroid: combined treatment with photodynamic therapy and aflibercept.

INTRODUCTION: To evaluate the effects of combined therapy using intravitreal Aflibercept (IVA) and photodynamic therapy (PDT) on polypoidal choroidal vasculopathy related to pachychoroid disease (PPCV). METHODS: Patients with PPCV were treated with PDT combined with 3 IVA injections on a monthly basis, followed by pro re nata criteria. The 12-month follow-up consisted of multiple revaluations of visual acuity and SS-OCT parameters of clinical activity. RESULTS: Nineteen eyes were included in the study; mean age was 65.5 years. Visual acuity improved after 12 months (0.35 ± 0.25 to 0.2 ± 0.20 logMAR, p = 0.005). Percentage of eyes with intraretinal and subretinal fluid reduced from baseline to the 12-month follow-up (from 52.6 to 10.5%, p = 0.12, and from 89.5 to 5.3% p = 0.0009, respectively). Central retinal and mean macular thicknesses reduced (258 ± 39.6 to 204.8 ± 38.8 µm p = 0.04 and 293.8 ± 32.1 to 248.1 ± 29.6 µm p = 0.017, respectively). Central choroidal and mean choroidal thicknesses also displayed a reduction (328.6 ± 54.9 to 289.8 ± 44.6 µm p = 0.001 and 314.5 ± 55.3 to 287.9 ± 47.6 µm p = 0.015, respectively). The mean number of injections was 4.6/year. CONCLUSION: The results support the use of a combined therapy with Aflibercept and PDT in PPCV. This treatment would act in synergy, with anti-VEGF controlling exudation and PDT closing the aneurysmal vessel and reducing choroidal congestion.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF PERIPAPILLARY MICROVASCULAR CHANGES AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To evaluate the radial peripapillary capillary plexus (RPCP) vessel density (VD) and the retinal nerve fiber layer (RNFL) thickness in eyes successfully treated with pars plana vitrectomy for primary rhegmatogenous retinal detachment. METHODS: In this cross-sectional multicenter clinical study, eyes with a minimum 12-month follow-up were reexamined. The RPCP VD and RNFL thickness in the rhegmatogenous retinal detachment subfields of the affected eye (study group) were compared with the corresponding areas of the healthy fellow eyes (control group). RESULTS: Fifty-three eyes were included in the study. A significantly lower RPCP VD and RNFL thickness were observed in those subfields affected by rhegmatogenous retinal detachment compared with those of the control group (P < 0.001). No statistically significant differences were observed between undetached subfields in the study group and their corresponding images in the control group. In the study group, a significant correlation was found between RPCP VD and RNFL thickness in subfields with detached retina (r = 0.393, P < 0.001) and undetached retina (r = 0.321, P < 0.001). CONCLUSION: Radial peripapillary capillary plexus VD changes were found in the subfields of detached retina successfully treated with pars plana vitrectomy and they correlated with RNFL thinning. These data suggest a coexistence of neuronal and microvascular damage in patients affected by rhegmatogenous retinal detachment.

Bilateral Ultrathin Descemet's Stripping Automated Endothelial Keratoplasty vs. Bilateral Penetrating Keratoplasty in Fuchs' Dystrophy: Corneal Higher-Order Aberrations, Contrast Sensitivity and Quality of Life.

Background and Objectives: The objective of this paper is to compare the visual outcomes and quality of life (QoL) after bilateral ultrathin Descemet's stripping automated endothelial keratoplasty (UT-DSAEK) with bilateral penetrating keratoplasty (PK) for Fuchs' endothelial dystrophy (FED). Materials and Methods: Retrospective comparative cohort study, including 11 patients with FED who underwent bilateral PK and 13 patients with FED who underwent bilateral UT-DSAEK. All patients were already pseudophakic or had undergone a combined cataract procedure. The main outcomes were corrected distance visual acuity (CDVA) corneal higher-order aberrations (HOAs), contrast sensitivity (CS) and quality of life (QoL). Results: The mean follow-up after the second eye surgery was 32.5 ± 10.2 months in PK and 19.6 ± 8.6 months in UT-DSAEK patients. The CDVA in the UT-DSAEK group was significantly better than in the PK one (0.18 ± 0.07 vs. 0.35 ± 0.16 logMAR, p < 0.0001). The mean anterior corneal total HOAs of the central 5 mm were significantly lower in UT-DSAEK eyes than in PK eyes (0.438 ± 0.078 µ and 1.282 ± 0.330 µ respectively, p < 0.0001), whilst the mean posterior total HOAs did not differ between groups (0.196 ± 0.056 µ and 0.231 ± 0.089 µ, respectively, p = 0.253). The CS was lower at 0.75 and 1.5 cycles/degree in P the K group when compared to the DSAEK one (p = 0.008 and 0.005, respectively). The QoL scores by the NEI RQL-42 test exhibited better values in DSAEK patients in 9 out of 13 scales. Conclusion: Our study confirms that UT-DSAEK provides a better visual function in terms of CDVA and CS, together with lower HOAs, when compared to PK. Hence, the vision-related QoL, binocularly evaluated by the NEI RQL-42 items, indicates a higher satisfaction in UT-DSAEK eyes.

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.

TGF-ß Serum Levels in Diabetic Retinopathy Patients and the Role of Anti-VEGF Therapy.

Transforming growth factor ß1 (TGFß1) is a proinflammatory cytokine that has been implicated in the pathogenesis of diabetic retinopathy (DR), particularly in the late phase of disease. The aim of the present study was to validate serum TGFß1 as a diagnostic and prognostic biomarker of DR stages. Thirty-eight subjects were enrolled and, after diagnosis and evaluation of inclusion and exclusion criteria, were assigned to six groups: (1) healthy age-matched control, (2) diabetic without DR, (3) non-proliferative diabetic retinopathy (NPDR) naïve to treatment, (4) NPDR treated with intravitreal (IVT) aflibercept, (5) proliferative diabetic retinopathy (PDR) naïve to treatment and (6) PDR treated with IVT aflibercept. Serum levels of vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF) and TGFß1 were measured by means of enzyme-linked immunosorbent assay (ELISA). Foveal macular thickness (FMT) in enrolled subjects was evaluated by means of structural-optical coherence tomography (S-OCT). VEGF-A serum levels decreased in NPDR and PDR patients treated with aflibercept, compared to naïve DR patients. PlGF serum levels were modulated only in aflibercept-treated NPDR patients. Particularly, TGFß1 serum levels were predictive of disease progression from NPDR to PDR. A Multivariate ANOVA analysis (M-ANOVA) was also carried out to assess the effects of fixed factors on glycated hemoglobin (HbA1c) levels, TGFß1, and diabetes duration. In conclusion, our data have strengthened the hypothesis that TGFß1 would be a biomarker and pharmacological target of diabetic retinopathy.

Infracyanine Green vs. Brilliant Blue G in Inverted Flap Surgery for Large Macular Holes: A Long-Term Swept-Source OCT Analysis.

Background and Objectives: To compare the long-term toxicity of infracyanine green (IFCG) to brilliant blue G (BBG) in inverted internal limiting membrane flap surgery (I-ILMFS) for large, full-thickness macular holes (FTMHs). Materials and Methods: Prospective randomized study including 39 eyes with ≥ 400 µm idiopathic FTMH who underwent I-ILMFS with either IFCG or BBG. Postoperative 6- and 12-month corrected distance visual acuity (CDVA), closure rate, and swept-source optical coherence tomography parameters, including ellipsoid zone (EZ) and external limiting membrane (ELM) mean defect length, central foveal thicknesses (CFT), parafoveal macular thickness (MT), ganglion cells and inner plexiform layer (GCL++) thickness, and peripapillary nerve fiber layer (pRNFL) thickness, were compared. Results: Nineteen eyes were included in the IFCG group and 20 eyes in the BBG group. In all cases a FTMH closure was found. CDVA improved at 6 and 12 months in both groups (p < 0.0005); the increase at 12 months was greater in the BBG group (p = 0.036). EZ and ELM defects did not differ between groups at either follow-up time. CFT at 12 months was greater in the BBG group (p = 0.041). A 12-months compared to 6-months MT decrease was present in both groups (p < 0.01). The GCL++ superior inner sector was thicker in the BBG group at 12 months (p = 0.036), as were the superior outer sector (p = 0.039 and p = 0.027 at 6 and 12 months, respectively) and inferior outer sector (p = 0.011 and p = 0.009 at 6 and 12 months, respectively). Conclusion: In our study BBG in I-ILMFS exhibits better long-term CDVA and retinal thickness than does IFCG, suggesting a lesser toxicity from BBG. These findings support the use of BBG over IFCG in I-ILMFS.

Solitary fibrous tumor of the orbital region: report of a case with emphasis on the diagnostic utility of STAT-6.

Solitary fibrous tumor (SFT) is a relatively rare soft tissue neoplasm originally described in the pleura. Since its first description, several cases arising in extra-pleural superficial and deep soft tissues have been reported in the literature. SFT arising in the head and neck region is quite rare, representing about the 6% of all SFTs, and the sinonasal tract is the most common involved region, followed by the orbit, the oral cavity and the salivary glands. Herein, we report the clinico-pathologic features of a rare case of SFT of the orbital region, emphasizing the diagnostic role of the immunomarker STAT-6. A 52-year-old female presented to our hospital with a nodular mass in the left orbital region. Histological examination revealed a uniformly hypercellular tumor composed of pale to slightly eosinophilic bland-looking spindle cells arranged in intersecting short fascicles with interspersed stellate-shaped, keloid-type collagen fibers. Notable hypocellular areas, perivascular hyalinization and hemangiopericytoma-like branching vascular pattern were absent. Immunohistochemically, neoplastic cells were diffusely positive for vimentin, CD34 and STAT-6. The introduction of STAT-6 in daily diagnostic practice is helpful to confidentially render a diagnosis of SFT even in the presence of unusual morphology and site.

PACAP through EGFR transactivation preserves human corneal endothelial integrity.

The corneal endothelium is composed of a single hexagonal-shaped cells layer adherent to the Descemet's membrane. The primary function of these cells is maintaining of tissue clarity by regulating its hydration. Trauma, aging or other pathologies cause their loss, counterbalanced by enlargement of survived cells unable to guarantee an efficient fluid pumping to and from the stroma. Regenerative medicine using human corneal endothelial cells (HCECs) isolated from peripheral corneal-scleral tissue of a donor could be an attractive solution, overcoming transplantation problems. In a previous study, we have demonstrated that HCECs treatment with pituitary adenylate cyclase-activating polypeptide (PACAP) following growth factors deprivation prevents their degeneration. However, the molecular mechanism mediating this effect has not been clarified, yet. Here, we have shown for the first time the expression of PACAP and its receptor (PAC1R) in human corneal endothelium and demonstrated that this peptide, selectively binding to PAC1R, induces epidermal growth factor receptor (EGFR) phosphorylation and the MAPK/ERK1/2 signaling pathway activation. In conclusion, our data have suggested that PACAP could represent an important trophic factor in maintaining human corneal endothelial integrity through EGFR transactivation. Therefore, PACAP, as well as epidermal growth factor and fibroblast growth factor, could co-operate to guarantee tissue physiological functioning by supporting corneal endothelial barrier integrity.

Intravitreal aflibercept for the treatment of radiation-induced macular edema after ruthenium 106 plaque radiotherapy for choroidal melanoma.

PURPOSE: To assess the efficacy of intravitreal aflibercept in patients suffering from post-radiation macular edema following plaque radiotherapy for choroidal melanoma. METHODS: This prospective, interventional case series included patients affected by radiation maculopathy (RM) with macular edema secondary to ruthenium-106 plaque brachytherapy for choroidal melanoma. The effect of intravitreal aflibercept on best-corrected visual acuity (BCVA), central foveal thickness (CFT) detected by spectral domain optical coherence tomography (sd-OCT), and Horgan's grading scale of RM was evaluated throughout the 24-month follow-up. Intraocular pressure (IOP) and possible complications were also recorded. RESULTS: Nine eyes of 9 patients were included. A mean of 4.4 ± 1.2 injections were given over the 24 months. At the end of follow-up, mean BCVA was significantly improved, from 0.9 ± 0.19 logMAR at baseline to 0.56 ± 0.3 logMAR (P = 0.028), and mean CFT was significantly decreased, from 546 ± 123 µm at baseline to 223 ± 34 µm (P < 0.001). Intravitreal aflibercept lowered baseline maculopathy stage as well. No significant change in IOP values and no complications, such as endophthalmitis, was recorded. CONCLUSION: Intravitreal aflibercept is an effective treatment for patients with radiation-induced macular edema, allowing functional and anatomical improvements to be achieved with a relatively low number of injections.

LATE-ONSET OCULAR HYPERTENSION AFTER VITRECTOMY: A Multicenter Study of 6,048 Eyes.

PURPOSE: To determine the incidence and risk factors for late-onset ocular hypertension (LOH) after vitrectomy. METHODS: From the electronic medical records of consecutive patients who underwent primary vitrectomy, from January 2010 to December 2015, at 5 tertiary vitreoretinal centers in Italy, patient demographics, systemic, ophthalmic, operative, and postoperative data were drawn. Main outcome measure was the presence of LOH, defined as intraocular pressure >21 mmHg detected more than 2 months after vitrectomy on at least 2 consecutive visits. RESULTS: Among 6,048 patients, LOH was found in 294 (4.9%) vitrectomized eyes and in 87 (1.4%) fellow eyes, (chi square; P < 0.001). Multivariable logistic regression showed that significant risk factors for developing LOH included intraoperative triamcinolone use (odds ratio [OR], 7.62; P < 0.001), longer axial length (OR, 1.55; P = 3.023), preoperative higher intraocular pressure (OR, 1.81; P = 0.003), and postvitrectomy pseudophakic/aphakic status (OR, 2.04; P < 0.001). Decision-tree analysis showed that the stronger predictor of LOH was intraoperative triamcinolone use (P < 0.001). Secondary predictors were a preoperative intraocular pressure more than 15 mmHg (P < 0.001) in eyes that use triamcinolone, and postvitrectomy pseudophakic/aphakic status (P = 0.007) in eyes that did not use triamcinolone. CONCLUSION: Late-onset ocular hypertension occurred in 4.9% of vitrectomized eyes. The main risk factors were intraoperative use of triamcinolone and postvitrectomy pseudophakic/aphakic status.

POOLED ESTIMATES OF INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.

PURPOSE: To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. METHODS: A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. RESULTS: From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. CONCLUSION: Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

DEXAMETHASONE INTRAVITREAL IMPLANT VS RANIBIZUMAB IN THE TREATMENT OF MACULAR EDEMA SECONDARY TO BRACHYTHERAPY FOR CHOROIDAL MELANOMA.

PURPOSE: To evaluate the efficacy of an intravitreal dexamethasone (Dex) implant 0.7 mg compared with intravitreal ranibizumab (Ra) for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma. METHODS: Eight patients were treated with intravitreal Ra, and eight patients received the Dex intravitreal implant. Visual acuity and foveal thickness were evaluated using spectral domain optical coherence tomography. RESULTS: The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the Ra group, a mean 7.8 ± 3.9 injections were given and the mean follow-up was 33 ± 15 months (range, 7-52 months). In the Dex group, a mean 2.1 ± 0.8 injections were given and the mean follow-up was 22 ± 7 months (range, 11-31 months). The mean visual acuity improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups from 459 ± 81 µm to 243 ± 58 µm and from 437 ± 71 µm to 254 ± 44 µm from the baseline to the last follow-up visit in the Ra and Dex groups, respectively. No patients developed significant cataract or ocular hypertension in both groups. CONCLUSION: Both Ra and Dex are effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. Dex-treated patients required fewer injections to achieve anatomical and functional improvement.

TRANSCONJUNCTIVAL NONVITRECTOMIZING VITREOUS SURGERY VERSUS 25-GAUGE VITRECTOMY IN PATIENTS WITH EPIRETINAL MEMBRANE: A Prospective Randomized Study.

PURPOSE: To compare the clinical outcomes and the rate of complications of 27-gauge transconjunctival nonvitrectomizing vitreous surgery (NVS) and of 25-gauge transconjunctival sutureless vitrectomy surgery for idiopathic epiretinal membrane removal. METHODS: In this prospective randomized study, 83 phakic eyes of 83 consecutive patients with an idiopathic epiretinal membrane were randomized to receive 27-gauge NVS (NVS-group) or 25-gauge vitrectomy (Standard-group). Main outcome measures were best-corrected visual acuity, central retinal thickness, nuclear density units' changes, and rate of complications. RESULTS: Thirty-nine eyes of the Standard-group and 40 of the NVS-group were considered in final analysis. Mean best-corrected visual acuity improved significantly in both groups, with a significant better result at 12 months in NVS-group (P = 0.039; t-test). Central retinal thickness decreased significantly in both groups (P < 0.001, Tukey test), without significant difference between the two groups at any time point. At 12 months, nuclear density increased significantly in the Standard-group (analysis of variance, P < 0.001), and it did not change in the NVS-group (analysis of variance, P = 0.537). Epiretinal membrane recurred in 5.1% of eyes in the Standard-group and in 7.5% of eyes in the NVS-group (Fisher's exact test, P = 1.000). CONCLUSION: The 27-gauge NVS is an effective surgical procedure in eyes with epiretinal membrane and it induces less progression of nuclear sclerosis than 25-gauge vitrectomy.

Diffusion-weighted magnetic resonance imaging and ultrasound evaluation of choroidal melanomas after proton-beam therapy.

PURPOSE: This study was undertaken to compare the ultrasound and magnetic resonance imaging parameters of ocular melanoma and to assess their variation after proton-beam therapy. MATERIALS AND METHODS: Fifteen choroidal melanoma patients treated with proton-beam therapy were enroled in the study. All patients underwent ophthalmologic evaluations, ultrasound, conventional magnetic resonance (MR) imaging and diffusion-weighted MR imaging before the start of therapy and 3 and 6 months after therapy. Basal diameters, thickness, internal reflectivity, tumour volumes and apparent diffusion coefficient (ADC) values of ocular melanomas were measured at each examination. Correlations between internal reflectivity and ADC were investigated. RESULTS: No significant changes were seen in tumour diameters and tumour height as assessed by B-scan and A-scan, respectively. Significant increase in mean tumour internal reflectivity was detected at 6 months (baseline 35 % ± 11; 6 months 48 % ± 8, Tukey-Kramer p = 0.005). On MRI, compared to baseline (mean 547 ± 262 mm(3)), a significant reduction in volume was seen at 6 months (Tukey-Kramer p = 0.045) (mean volume 339 ± 170 mm(3), mean reduction 38 %). A significant increase in ADC (baseline 1,002 ± 109 mm(2)/s) was detected both at 3 and 6 months after proton therapy (respectively, 1,454 ± 90 and 1,833 ± 261 mm(2)/s, both p < 0.001). CONCLUSIONS: By MRI, in particular by ADC assessment, it is possible to detect early variations in melanoma treated by proton-beam therapy. This examination could be used together with ultrasound in the follow-up of this treatment.

Correlation of preoperative retinal pigment epithelium status with foveal microstructure in repaired macular holes.

PURPOSE: To investigate, with spectral-domain optical coherence tomography, if the preoperative status of the retinal pigment epithelium (RPE) affects the postoperative foveal morphology and visual outcomes in eyes with surgically closed macular holes (MHs). METHODS: In 52 eyes with surgically closed MHs, preoperative RPE morphology was evaluated and graded based on the measurement of the largest hyperreflective protrusions above the RPE line. Foveal microstructural features and best-corrected visual acuity (BCVA) were evaluated 12 months after surgery. RESULTS: At 12 months, a significant correlation was found between postoperative degree of integrity of the photoreceptors with preoperative RPE morphology, and base diameter of the hole (p = 0.003 and p = 0.028, respectively); mean BCVA at 12 months in eyes with diffuse RPE alteration was significantly lower than in eyes with small or no RPE alteration (p < 0.05). CONCLUSIONS: Preoperative RPE integrity may be indicative of good photoreceptor restoration and visual recovery in patients with surgically closed MHs.

Enhancing Diabetic Macular Edema Treatment Outcomes: Exploring the ESASO Classification and Structural OCT Biomarkers.

INTRODUCTION: This study assessed the European School of Advanced Studies in Ophthalmology (ESASO) classification's prognostic value for diabetic macular edema (DME) in predicting intravitreal therapy outcomes. METHODS: In this retrospective, multicenter study, patients aged > 50 years with type 1 or 2 diabetes and DME received intravitreal antivascular endothelial growth factor (anti-VEGF) agents (ranibizumab, bevacizumab, and aflibercept) or steroids (dexamethasone). The primary outcome was visual acuity (VA) change post-treatment, termed as functional response, measured 4-6 weeks post-third anti-VEGF or 12-16 weeks post-steroid injection, stratified by initial DME stage. RESULTS: Of the 560 eyes studied (62% male, mean age 66.7 years), 31% were classified as stage 1 (early), 50% stage 2 (advanced), 17% stage 3 (severe), and 2% stage 4 (atrophic). Visual acuity (VA; decimal) improved by 0.12-0.15 decimals in stages 1-2 but only 0.03 decimal in stage 3 (all p < 0.0001) and 0.01 in stage 4 (p = 0.38). Even in eyes with low baseline VA ≤ 0.3, improvements were significant only in stages 1 and 2 (0.12 and 0.17 decimals, respectively). Central subfield thickness (CST) improvement was greatest in stage 3 (-229 µm, 37.6%, p < 0.0001), but uncorrelated with VA gains, unlike stages 1 and 2 (respectively: -142 µm, 27.4%; - 5 µm, 12%; both p < 0.0001). Stage 4 showed no significant CST change. Baseline disorganization of retinal inner layers and focal damage of the ellipsoid zone/external limiting membrane did not influence VA improvement in stages 1 and 2. Treatment patterns varied, with 61% receiving anti-VEGF and 39% dexamethasone, influenced by DME stage, with no significant differences between therapeutic agents. CONCLUSION: The ESASO classification, which views the retina as a neurovascular unit and integrates multiple biomarkers, surpasses single biomarkers in predicting visual outcomes. Significant functional improvement occurred only in stages 1 and 2, suggesting reversible damage, whereas stages 3 and 4 likely reflect irreversible damage.

The genomic mosaic of mitochondrial dysfunction: Decoding nuclear and mitochondrial epigenetic contributions to maternally inherited diabetes and deafness pathogenesis.

Aims: Maternally inherited diabetes and deafness (MIDD) is a complex disorder characterized by multiorgan clinical manifestations, including diabetes, hearing loss, and ophthalmic complications. This pilot study aimed to elucidate the intricate interplay between nuclear and mitochondrial genetics, epigenetic modifications, and their potential implications in the pathogenesis of MIDD. Main methods: A comprehensive genomic approach was employed to analyze a Sicilian family affected by clinically characterized MIDD, negative to the only known causative m.3243 A > G variant, integrating whole-exome sequencing and whole-genome bisulfite sequencing of both nuclear and mitochondrial analyses. Key findings: Rare and deleterious variants were identified across multiple nuclear genes involved in retinal homeostasis, mitochondrial function, and epigenetic regulation, while complementary mitochondrial DNA analysis revealed a rich tapestry of genetic diversity across genes encoding components of the electron transport chain and ATP synthesis machinery. Epigenetic analyses uncovered significant differentially methylated regions across the genome and within the mitochondrial genome, suggesting a nuanced landscape of epigenetic modulation. Significance: The integration of genetic and epigenetic data highlighted the potential crosstalk between nuclear and mitochondrial regulation, with specific mtDNA variants influencing methylation patterns and potentially impacting the expression and regulation of mitochondrial genes. This pilot study provides valuable insights into the complex molecular mechanisms underlying MIDD, emphasizing the interplay between nucleus and mitochondrion, tracing the way for future research into targeted therapeutic interventions and personalized approaches for disease management.