Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus.

PURPOSE: To compare clinical outcomes of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) and standard corneal cross-linking (standard CL) for the treatment of progressive keratoconus 12 months after the operation. DESIGN: Prospective randomized controlled clinical trial. PARTICIPANTS: Thirty-four eyes of 25 participants with progressive keratoconus were randomized into T-ionto CL (22 eyes) or standard CL (12 eyes). METHODS: T-ionto CL was performed using an iontophoresis device with dextran-free 0.1% riboflavin-5-phosphate solution with enhancers and by irradiating the cornea with a 10 mW/cm2 ultraviolet A device for 9 minutes. Standard CL was performed according to the Dresden protocol. MAIN OUTCOME MEASURES: The primary outcome measure was stabilization of keratoconus after 12 months through analysis of maximum simulated keratometry readings (Kmax, diopters). Other outcome measures were corrected distance visual acuity (CDVA, logarithm of the minimum angle of resolution [logMAR]), manifest spherical equivalent refraction (D), central corneal thickness (CCT, micrometers) and endothelial cell density (ECD). Follow-up examinations were arranged at 3 and 7 days and 1, 3, 6, and 12 months. RESULTS: Twelve months after T-ionto CL and standard CL, Kmax on average flattened by -0.52±1.30 D (P = 0.06) and -0.82±1.20 D (P = 0.04), respectively. The mean change in CDVA was -0.10±0.12 logMAR (P = 0.003) and -0.03±0.06 logMAR (P = 0.10) after T-ionto CL and standard CL, respectively. The manifest spherical equivalent refraction changed on average by +0.71±1.44 D (P = 0.03) and +0.21±0.76 D (P = 0.38), respectively. The CCT and ECD measures did not change significantly in any group at 12 months. Significant differences in the outcome measures between treatments were found in the first week postoperatively. No complications occurred in the T-ionto CL group; 1 eye (8%) had sterile corneal infiltrates, which did not affect the final visual acuity, in the standard CL group. CONCLUSIONS: Significant visual and refractive improvements were found 12 months after T-ionto CL, though the average improvement in corneal topography readings was slightly lower than the Dresden protocol in the same period.

HIGH-RESOLUTION MULTIMODAL IMAGING AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To investigate the changes of the vitreomacular interface during a 1-year follow-up after idiopathic epiretinal membrane (iERM) surgery. METHODS: Six patients affected by fovea-attached iERM were recruited in this pilot study. Pars plana vitrectomy associated with epiretinal membrane peeling was performed uneventfully in all cases. In four cases, the inner limiting membrane was removed using Brilliant blue G. En face high-resolution adaptive optics and cross-sectional spectral domain optical coherence tomography retinal imaging were performed before and at 1, 3, 6, and 12 months after surgery. The microstructures of vitreomacular interface in high-resolution adaptive optics images were correlated to the cross-sectional spectral domain optical coherence tomography data. RESULTS: Preoperatively, adaptive optics images showed multiple abnormalities of the vitreomacular interface, such as macrofolds, microfolds, and hyperreflective microstructures. We identified two subtypes of iERM according to the distribution of microfolds over the foveal area, which included the radial-type and the grid-type iERM. After surgery, the morphology of the vitreomacular interface changed compared with the preoperative state. The number of both macrofolds and microfolds was reduced in all cases. The hyperreflective structures were still resolvable in all cases, however presenting different shape and morphology than preoperatively. In addition, they showed marked differences between eyes that had internal limiting membrane removal and eyes that did not. CONCLUSION: Adaptive optics imaging gives new insight into the changes of vitreomacular interface after iERM surgery. Enhanced multimodal imaging of the vitreomacular interface and retinal structures can be valuable to monitor treatment outcome of iERM.

Multifocal VEP provide electrophysiological evidence of predominant dysfunction of the optic nerve fibers derived from the central retina in Leber's hereditary optic neuropathy.

PURPOSE: To differentiate the bioelectrical cortical responses driven by axons from central and mid-peripheral retina in Leber's hereditary optic neuropathy (LHON) by using multifocal visual evoked potentials (mfVEP). METHODS: Seventeen genetically confirmed LHON patients (33.35 ± 8.4 years, 17 eyes) and 22 age-matched controls (C) (38.2 ± 6.0 years, 22 eyes) were studied by mfVEP and optical coherence tomography. MfVEP P1 implicit time (P1 IT, ms) and response amplitude density of the N1-P1 components (N1-P1 RAD, nV/deg(2)) of the second order binary kernel were measured for five concentric retinal areas between the fovea and mid-periphery: 0-20 degrees (R1 to R5). RESULTS: Mean mfVEP P1 ITs and N1-P1 RADs at all five foveal eccentricities were significantly different (p < 0.01) in LHON when compared to controls. In both groups, mean mfVEP responses obtained from R1 to R5 showed a progressive shortening of P1 ITs (linear fitting, LHON: r = -0.95; C: r = -0.98) and decrease of N1-P1 RADs (exponential fitting, LHON: r (2) = 0.94; C: r (2) = 0.93). The slope of the linear fitting between mean mfVEP P1 ITs in the two groups was about three times greater in LHON than in controls (LHON: y = -13.33x +182.03; C: y = -4.528x +108.1). MfVEP P1 ITs detected in R1 and R2 (0-5 degrees) were significantly correlated (p < 0.01) with the reduction of retinal nerve fiber layer thickness of the temporal quadrant. CONCLUSIONS: MfVEP identifies abnormal neural conduction along the visual pathways in LHON, discriminating a predominant involvement of axons driving responses from the central retina when compared to those serving the mid-peripheral retina.

Repeatability of Automatic Measurements by an Anterior Segment Swept-Source OCT Biometer in Patients With Keratoconus.

PURPOSE: To evaluate the repeatability of automatic measurements of a new anterior segment optical coherence tomographer (ANTERION; Heidelberg Engineering) and their agreement with an anterior segment optical coherence tomography device combined with Placido disc corneal topography (MS-39; CSO) in patients affected by keratoconus. METHODS: Fifty-four consecutive patients were included. Three measurements were performed with the ANTERION and one with the MS-39. Repeatability was assessed by means of within-subject standard deviation, coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Agreement was investigated with the 95% limits of agreement. The paired t-test and Wilcoxon matched-pairs test were performed to compare the measurements of the different devices. RESULTS: Repeatability of ANTERION measurements was high, with an ICC greater than 0.98 for all parameters. Many parameters revealed a CoV of less than 1% and a CoV within 5% was obtained for astigmatism measurements. The ANTERION measured a significantly higher corneal power and the MS-39 more negative posterior keratometric values. These differences were mirrored by a moderate agreement for mean simulated keratometry and poor agreement for total corneal power and posterior keratometry. CONCLUSIONS: The ANTERION revealed high repeatability of automatic measurements and good agreement with the MS-39 for many parameters in patients affected by keratoconus, but for most parameters the two instruments cannot be considered interchangeable. [J Refract Surg. 2024;40(7):e445-e452.].

Prognostic Imaging Biomarkers in Diabetic Macular Edema Eyes Treated with Intravitreal Dexamethasone Implant.

BACKGROUND: The aim was to evaluate predictive value of baseline optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in diabetic macular edema (DME) treated with dexamethasone implant (DEXi). METHODS: OCT and OCTA parameters were collected: central macular thickness (CMT), vitreomacular abnormalities (VMIAs), intraretinal and subretinal fluid (mixed DME pattern), hyper-reflective foci (HRF), microaneurysms (MAs) reflectivity, ellipsoid zone disruption, suspended scattering particles in motion (SSPiM), perfusion density (PD), vessel length density, and foveal avascular zone. Responders' (RES) and non-responders' (n-RES) eyes were classified considering morphological (CMT reduction ≥ 10%) and functional (BCVA change ≥ 5 ETDRS letters) changes after DEXi. Binary logistic regression OCT, OCTA, and OCT/OCTA-based models were developed. RESULTS: Thirty-four DME eyes were enrolled (18 treatment-naïve). OCT-based model combining DME mixed pattern + MAs + HRF and OCTA-based model combining SSPiM and PD showed the best performance to correctly classify the morphological RES eyes. In the treatment-naïve eyes, VMIAs were included with a perfect fit for n-RES eyes. CONCLUSION: The presence of DME mixed pattern, a high number of parafoveal HRF, hyper-reflective MAs, SSPiM in the outer nuclear layers, and high PD represent baseline predictive biomarkers for DEXi treatment responsiveness. The application of these models to treatment-naïve patients allowed a good identification of n-RES eyes.

In vivo assessment of associations between photoreceptors structure and macular perfusion in type 1 diabetes.

PURPOSE: To explore the potential relationships between macular vascular network and different adaptive optics (AO) metrics in patients with type 1 diabetes mellitus (DM1) with no signs (NoDR) or mild non-proliferative diabetic retinopathy (NPDR). DESIGN: Observational cross-sectional study. METHODS: Forty eyes of consecutive patients with DM1 (12 NoDR and 28 NPDR) and 10 healthy age-matched control subjects were included. All patients and controls were imaged using AO retinal camera and PLEX Elite 9000 optical coherence tomography (OCT) angiography (OCTA). The AO outcome measures to evaluate the cone photoreceptor mosaic characteristics were as follows: (1) Cone density (CD); (2) Linear Dispersion Index (LDi) and (3) Heterogeneity Packing Index (HPi). The OCTA outcome measures included: (1) superficial capillary plexus (SCP) perfusion density (PD); (2) deep capillary plexus (DCP) PD and (3) the choriocapillaris (CC) flow deficit percentage (FD%). RESULTS: NPDR group exhibited a close relationship between cone metrics and CC FD. Notably, CC FD% increase along with LDi (p=0.035), while the increasing CC FD% were associated with reducing CD (p=0.042) and the HPi (p=0.017). Furthermore, the OCTA parameters, including PD SCP and DCP, showed a significant negative correlation with CD. CONCLUSIONS: Our results demonstrated the relationship between macular perfusion at both retinal and choroidal levels and the cone mosaic in patients with DM1 interpolating swept-source-OCTA and AO metrics. In NPDR eyes, the photoreceptor damage was accompanied by CC insufficiency since the early stages of the disease.

Progression Biomarkers of Microvascular and Photoreceptor Changes Upon Long-Term Evaluation in Type 1 Diabetes.

Purpose: To assess demographic, metabolic, and imaging predictors influencing microvasculature and photoreceptors changes over a 4-year follow-up in type 1 diabetes mellitus (DM1). Methods: This prospective cohort study enrolled patients with DM1 with mild non-proliferative diabetic retinopathy. Complete medical records, glycosylated hemoglobin (HbA1c), optical coherence tomography angiography, and adaptive optics were collected for the 4 years of follow-up. The main outcome measures included perfusion density at the superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris (CC) flow deficits (FDs, %), cone density, linear dispersion index (LDi), and heterogeneity packing index (HPi). Results: The SCP presented a dichotomic perfusion trend, with increasing PD at 1 and 2 years and a subsequent decline (P < 0.001). DCP presented a similar trend in the first 2 years (P < 0.01) but not at the following time points, whereas CC FDs constantly increased over time (P < 0.01). The best-fitted model for the microvascular parameters demonstrated that the main factors affecting SCP included time (P < 0.001), duration of diabetes (P = 0.007), and HbA1c (P = 0.03), whereas the DCP was influenced by LDi modifications (P = 0.006). The LDi and HPi were mainly influenced by SCP and CC perfusion in the parafovea (P = 0.02). Conclusions: This study demonstrated an initial vasodilatory phenomenon resulting from a compensatory mechanism from the superficial vasculature, followed by capillary dropout. Initially, it would seem that there was an adaptive response by the DCP to the needs of the photoreceptors. Although the SCP may initially support the DCP, when the microvascular damage becomes diffuse and involves the SCP and CC it directly affects photoreceptor integrity.

Differences in cysts characteristics and related influence on the anatomical response after dexamethasone implant in diabetic macular oedema.

PURPOSE: To assess the clinical significance of suspended scattering particles in motion (SSPiM) and different cystic phenotypes in diabetic macular oedema (DME) treated with dexamethasone implant (DEX-i). METHODS: A retrospective review of type 2 diabetic patients with DME treated with a DEX-i was conducted. Swept-source optical coherence tomography angiography (OCTA, PLEX Elite 9000) with a 3-mm volume cube was performed. Regions of interest were delineated with Fiji software (version 2.1.0/1.53.c) in the superficial vascular complex (SVC) and deep capillary plexus (DCP) at baseline, 2- and 4-months after DEX-i. SSPiM was defined as regions of variable reflectivity with a decorrelation signal. Without a detectable decorrelation signal, its counterpart was addressed as 'corpuscular,' while hyporeflective cysts were optical empty without hyperreflective material enclosed. RESULTS: After treatment, the hyporeflective component demonstrated substantial reabsorption in the SVC (-95.4% at 2- and -84.4% at 4-months, p < 0.01 both) and DVC (-84.4%, 2-months), with a less critical decrease of the corpuscular component in the SVC (2-months: -41.9%, p = 0.001 and 4 months: -1.8%, p = 0.73), and not significant in the DVC. SSPiM did not significantly change in the SVC and DVC neither at 2- and 4-months (p > 0.05, all). CONCLUSIONS: After a single DEX-i, the clearance of different cystic phenotypes proceeds with resorption of hyporeflective, followed by corpuscular components. SSPiM demonstrated minimal response, indicating a severe BRB breakdown that may require repeated treatment to reach a satisfactory anatomical response.

Impact of Intravitreal Anti-VEGF Therapy on Microperimetry of the Retinal Nonperfusion Areas of Patients with Proliferative Diabetic Retinopathy.

INTRODUCTION: This study assessed retinal nonperfusion area (NPA) changes after anti-VEGF treatment in proliferative diabetic retinopathy (PDR) eyes using swept-source widefield optical coherence tomography angiography (SS-WF OCTA) and investigated the relationships with the microperimetry (MP-1) functional changes observed in the same areas. METHODS: This was a single-center observational case series. Seven PDR eyes naïve to treatment that received three monthly intravitreal injections of aflibercept were included. All eyes were imaged with SS-WF OCTA and MP-1 at baseline (T0) and 1 month after the third injection (T1). The regions of interest (ROIs) with evidence of NPAs at T0 OCTA images were selected. Qualitative and quantitative [perfusion density (PD) and vessel length density (VLD)] OCTA vascular changes in the selected ROIs between T0 and T1 were compared with the corresponding MP-1 functional changes [mean sensitivity (MS)]. RESULTS: Twenty-five ROIs were selected. In 52% of the ROIs, an improvement in MS was observed at T1, which was associated with qualitative and quantitative improvement in 92.3% of NPAs by OCTA. In 32% of the ROIs, MS worsening was observed at T1, which was associated with qualitative and quantitative worsening in 75% of NPAs by OCTA. Positive correlations between MS and both PD and VLD were found. Fisher's test showed an association between the improvements in MP and VLD. CONCLUSIONS: An association between OCTA and MP-1 parameter changes was found. The concomitant functional and morphological improvement in half of the ROIs suggests that anti-VEGF treatment may promote retinal changes that result in a better functional response.

A Novel Algorithm for the Evaluation of Corneal Nerve Beadings by in vivo Confocal Microscopy in Patients With Type 1 Diabetes Mellitus.

Purpose: Peripheral neuropathy could complicate diabetes mellitus (DM). In vivo confocal microscopy (IVCM) is an ocular examination for the diagnosis of small fiber neuropathies and the detection of the earliest corneal sub-basal nerve plexus (SBP) alterations. Corneal SBP characteristics include focal enlargement along with the nerve fiber, called corneal beadings. These dilatations represent a mitochondrial accumulation induced by the reactive oxygen stress, as a consequence of hyperglycemia. For this reason, corneal beadings are considered indicative of metabolic activity. This study aimed to describe the corneal characteristics of a population of type 1 diabetes mellitus (T1DM) well metabolically controlled, using a new algorithm for the analysis of corneal beading size (BS). Methods: Patients aged ≥18 years affected by T1DM were compared with healthy subjects who underwent IVCM (Confoscan 4; Nidek Technologies Padova, Italy). Starting from the coordinates of the beadings detected by the IVCM, we implemented a new algorithm for automatically measuring BS in corneal SBP images. Results: We compared 20 eyes of T1DM patients with 26 healthy controls. The corneal nerves' fiber length (p = 0.008), corneal nerves' fiber length density (p = 0.008), and the number of fibers (p = 0.017) were significantly lower in the diabetic group compared with controls. There was no difference between diabetic and healthy eyes in the mean number of corneal beadings both in the frame of analysis (p = 0.606) and for 0.1 mm of SBP nerve (p = 0.145). Regarding the BS, patients with T1DM had corneal beadings larger than controls (p = 0.036). Conclusions: We found that the corneal beadings parameters are similar in healthy and T1DM individuals. Nevertheless, measuring the BS with our algorithm, we showed that corneal beadings are enlarged in patients affected by T1DM when compared with healthy controls. Identifying beading expansion in corneal nerve fiber using IVCM should become a useful tool to predict peripheral neuropathy at an early stage.

Viral Acute Anterior Uveitis: Clinical Signs Useful for Differential Diagnosis.

Purpose: To assess the frequency of clinical signs in patients with viral acute anterior uveitis (AAU), and their ability to differentiate viral versus non-viral AAU.Methods: 168 patients with AAU, including 84 with presumed viral etiology, were evaluated. Sensitivity, specificity, area under the curve (AUC), positive and negative predictive value were calculated for each clinical sign. The model built with these parameters was tested on a validation group comprising 66 patients with AAU.Results: The most useful clinical signs were unilaterality (sensitivity: 98.8%, specificity: 57.1%), intraocular pressure (IOP) ≥24 mmHg (sensitivity: 68.7%, specificity: 91.7%), and the association between the two (sensitivity: 68.7%, specificity: 95.2%). In the validation group, the model built with these parameters presented AUC of 0.939. Adding iris atrophy AUC increased to 0.97. Considering these signs, it was possible to diagnose viral uveitis in 93.9% of the patients.Conclusion: Unilaterality, IOP≥24 mmHg and iris atrophy are significant predictors of possible viral etiology in AAU.

Imaging Biomarkers of 1-Year Activity in Type 1 Macular Neovascularization.

Purpose: The purpose of this study was to evaluate the predictive value of optical coherence tomography (OCT) and OCT angiography (OCTA) parameters at baseline on lesion's activity at the 1-year follow-up in type 1 macular neovascularizations (MNVs) treated with 1-year fixed regimen of intravitreal aflibercept injections (q8 IAIs). Methods: All patients were imaged by structural OCT to evaluate central macular thickness (CMT), subretinal fluid (SRF), subretinal hyper-reflective material (SHRM), intraretinal fluid (IRF) and intraretinal hyper-reflective dots (HRDs), and by Swept-Source OCTA to measure baseline MNV area, perfusion density (PD), vessel length density (VLD), and vessel diameter index. At the end of q8 IAI, patients were classified in two groups: active-MNV (A-MNV) and inactive-MNV (I-MNV), considering the OCT signs of activity. Three binary logistic regression models were developed: (1) OCT-based, (2) OCTA-based, and (3) OCT/OCTA-based model. Results: Thirty-one treatment-naïve type 1 MNVs were enrolled (13 A-MNV and 18 I-MNV). No differences were observed in baseline OCT and OCTA characteristics between A-MNV and I-MNV. Among the models developed, model 3 that combined OCT/OCTA parameters showed a performance of 87.5% and excellent sensitivity for A-MNV lesions (100%). By analyzing the model, the A-MNV group appears more likely to show at baseline SRF, greater CMT, wider MNV area, and lower PD and VLD compared to I-MNV. Conclusions: Our study demonstrated that the combination of baseline OCT and OCTA parameters allowed to achieve a good models' performance in the prediction of MNV activity permitting to correctly classifying the active lesions at the end of follow-up period, with excellent sensitivity. Translational Relevance: OCT/OCTA could integrate statistical models potentially useful for artificial intelligence.

To compare corneal confocal microscopy of eyes with Fuchs' endothelial corneal dystrophy after two different endothelial surgeries.

PURPOSE: To study the features of corneal confocal microscopy of eyes with Fuchs' endothelial corneal dystrophy (FECD) after successful Descemet stripping automated endothelial keratoplasty (DSAEK) versus Descemet membrane endothelial keratoplasty (DMEK). METHODS: Thirty-two eyes affected by FECD with corneal oedema requiring a corneal graft were treated with DSAEK (15 eyes) or DMEK (17 eyes). All patients underwent in vivo corneal confocal microscopy (IVCCM) at 6 months postoperatively. We evaluated preoperative and postoperative corrected distance visual acuity (CDVA) and the correlation with IVCCM characteristics. RESULTS: Using IVCCM, Z-scan curve analysis showed similar subepithelial reflectivity peaks between the two groups (DSAEK 1256 SU ± 514 vs DMEK 1118 SU ± 408, p = 0.411), while the interface reflectivity was significantly higher in the DMEK group (1511 SU ± 357) than in the DSAEK group (1029 SU ± 413, p = 0.002). CONCLUSION: Comparing the corneal confocal microscopic characteristics after DMEK with those after DSAEK and their correlation with visual outcome at 6 months, we hypothesized that the presence of a third reflectivity peak in the Z-scan curves of DSAEK patients could justify the poorer visual outcome with this endothelial surgery than with DMEK.

Corneal Subbasal Plexus in Eyes with Fuchs' Endothelial Corneal Dystrophy after Two Different Endothelial Surgeries.

PURPOSE: To evaluate the morphological features and density of corneal subbasal plexus (SBP) using in vivo corneal confocal microscopy (IVCCM) in patients affected by Fuchs' endothelial corneal dystrophy (FECD) six months after Descemet membrane endothelial keratoplasty (DMEK) and Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: We included patients affected by FECD, requiring corneal endothelial surgery due to corneal oedema occurred from 3 to 6 months. 7 eyes underwent DMEK and 7 eyes DSAEK. All patients performed IVCCM preoperative and in six months postoperative. We analyzed SBP parameters, using CS4 Nerves Tracking Tool, and we studied the differences between the two endothelial keratoplasties. RESULTS: Comparing the eyes treated with DMEK with those treated with DSAEK, preoperative corneal thickness, corrected distance visual acuity (CDVA), and age were similar in both groups. SBP was not detectable at preoperative IVCCM in any eye. Postoperatively, the nerve fibers length, the nerve fibers density, the tortuosity, and the number of fibers and of branching did not differ in the eyes that underwent DMEK compared to DSAEK. The corneal beadings density was higher after DMEK than DSAEK, and this difference was statistically significant (P = 0.004). The type of endothelial keratoplasty was not associated with the presence or absence of postoperative corneal SBP (Pearson' chi-square, 0.755). CONCLUSIONS: Postoperative corneal reinnervation should be easily and noninvasively studied using IVCCM. Morphological postoperative features of SBP did not differ between two different types of endothelial keratoplasty, DMEK and DSAEK, despite the different sizes of the corneal incision. The lower beading density in the DSAEK group should be the consequence of a different distribution of mitochondria along the nerve fibers, as expression of a supposed higher metabolic distress in the DSAEK group.

Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 3-year Pilot Study Evaluating Morpho-Functional Retinal Changes.

INTRODUCTION: This study aimed to evaluate the effect of treatment with eye drops containing citicoline and vitamin B12 on changes in function of the inner retina, morphology of the inner and outer retina, and microvascular condition in patients with type 1 diabetes (DM1) with mild signs of non-proliferative diabetic retinopathy (NPDR) during 3 years of follow-up. METHODS: A pilot study with prospective, randomized, and double-masked design was conducted to address the aims. Twenty patients with DM1 were enrolled and randomly divided into two groups: the DC group comprising patients treated with citicoline and vitamin B12 eye drops (10 patients; mean age ± standard deviation, 46.86 ± 8.78 years) and the DP group comprising those treated with placebo (10 patients; mean age ± standard deviation, 47.89 ± 7.74 years). In the DC group, one eye of each patient was treated with citicoline and vitamin B12 eye drops (OMK2®, Omikron Italia srl, Italy, 3 drops/day), while in the DP group, it was treated with placebo (eye drops containing hypromellose 0.3%, 3 drops/day) for a 3-year period. In both groups, Humphrey Matrix frequency doubling technology (FDT), spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA), and adaptive optics (AO) were applied at baseline and 12, 24, and 36 months of the follow-up period. RESULTS: In the results of follow-up evaluation, the DC and DP groups were significantly different: Significant reduction in function in terms of 10-2 FDT mean sensitivity and in morphology reflected by an increase in inner nuclear layer thickness and decrease in other plexiform layer thickness and foveal vessel density were observed in the DP group, while no such significant changes were observed in the DC group in the long term. CONCLUSIONS: This pilot study indicated that patients with DM1 with mild signs of diabetic retinopathy (DR) who underwent treatment with citicoline and vitamin B12 eye drops for a 3-year duration achieved stabilization or decreased rate of functional impairment, neuroretinal degeneration, and microvascular damage. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04009980.

Optical Coherence Tomography Angiography Findings in Active and Inactive Ocular Behçet Disease.

PURPOSE: To study macular microvascular changes in ocular Behçet disease (OBD) using optical coherence tomography angiography (OCTA). METHODS: Quantitative and qualitative analyses of OCTA were performed on 23 OBD patients with active or inactive uveitis and compared with healthy controls. RESULTS: Deep capillary plexus (DCP) is the most frequently involved in OBD (p < 0.001). Its vessel density (VD) is reduced compared with controls in both active (p < 0.007) and inactive uveitis (p = 0.03). In inactive uveitis, VD is inversely related to the number of uveitis relapses (superficial capillary plexus: r = -0.694, p = 0.004; DCP: r = -0.541, p = 0.037) and it is significantly reduced in patients with a uveitis-free period ≥5 years compared with healthy controls (p < 0.038). CONCLUSIONS: Macular VD is reduced in Behçet patients with active and inactive uveitis, especially in DCP. In inactive uveitis, VD is inversely related to the number of ocular relapses and cannot be restored during time.

Baseline SD-OCT characteristics of diabetic macular oedema patterns can predict morphological features and timing of recurrence in patients treated with dexamethasone intravitreal implants.

AIMS: To evaluate the timing and spectral-domain optical coherence tomography (SD-OCT) features of diabetic macular oedema (DME) recurrence according to baseline OCT patterns in patients treated with dexamethasone implant (DEX-I). METHODS: This is a retrospective observational study (72 eyes/65 patients). Best-corrected visual acuity, timing of DME recurrence, and SD-OCT pattern [intraretinal cysts (IRC), IRC plus subretinal fluid (mixed), external limiting membrane (ELM), ellipsoid (IS/OS) layer integrity] were assessed at baseline and monthly until first DME recurrence. RESULTS: Forty-two (58.3%) and 30 (41.6%) DME eyes had an IRC and mixed DME pattern at baseline, respectively. Twenty-four out of thirty mixed eyes (80%) relapsed without subretinal fluid. At baseline, mixed eyes showed similar changes in ELM and IS/OS (60 and 76.6% of eyes, respectively) versus IRC eyes (42.8 and 80.9% of eyes). After DME recurrence, more mixed eyes at baseline showed ELM and IS/OS changes (63.3 and 86.6%) than IRC eyes (50 and 76.2%). 33.3% of mixed eyes had DME recurrence at ≥ 6 months from first DEX-I implant versus 19% of IRC eyes. CONCLUSIONS: Mixed DME eyes were treated with DEX-I relapse later and more frequently without subretinal fluid than IRC eyes. SD-OCT characteristics of different DME patterns at baseline can predict morphological features and timing of DME recurrence.

Early Alterations of Corneal Subbasal Plexus in Uncomplicated Type 1 Diabetes Patients.

PURPOSE: The purpose of our study is to describe the in vivo corneal confocal microscopy characteristics of subbasal nerve plexus in a highly selected population of patients affected by type 1 diabetes mellitus (T1DM) without any microvascular diabetes complications. METHODS: We included 19 T1DM patients without diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria. All patients underwent in vivo corneal confocal microscopy and blood analysis to determine subbasal nerve plexus parameters and their correlation with clinical data. We compared the results with 19 healthy controls. RESULTS: The T1DM group showed a significant decrease of the nerve fiber length (P=0.032), the nerve fiber length density (P=0.034), the number of fibers (P=0.005), and the number of branchings (P=0.028), compared to healthy subjects. The nerve fiber length, nerve fiber length density, and number of fibers were directly related to the age at onset of diabetes and inversely to the duration of DM. BMI (body mass index) was highly related to the nerve fiber length (r = -0.6, P=0.007), to the nerve fiber length density (r = -0.6, P=0.007), and to the number of fibers (r = -0.587, P=0.008). No significant correlations were found between the corneal parameters and HbA1c. CONCLUSIONS: Early subclinical fiber corneal variation could be easily detected using in vivo corneal confocal microscopy, even in type 1 diabetes without any microvascular diabetes complications, including diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria.

Reliability and Agreement Between Metrics of Cone Spacing in Adaptive Optics Images of the Human Retinal Photoreceptor Mosaic.

Purpose: To assess reliability and agreement among three metrics used to evaluate the distribution of cell distances in adaptive optics (AO) images of the cone mosaic. Methods: Using an AO flood illumination retinal camera, we acquired images of the cone mosaic in 20 healthy subjects and 12 patients with retinal diseases. The three spacing metrics studied were the center-to-center spacing (Scc), the local cone spacing (LCS), and the density recovery profile distance (DRPD). Each metric was calculated in sampling areas of different sizes (64 × 64 µm and 204 × 204 µm) across the parafovea. Results: Both Scc and LCS were able to discriminate between healthy subjects and patients with retinal diseases; DRPD did not reliably detect any abnormality in the distribution of cell distances in patients with retinal diseases. The agreement between Scc and LCS was high in healthy subjects (intraclass correlation coefficient [ICC] ≥ 0.79) and moderate in patients with retinal diseases (ICC ≤ 0.51). The DRPD had poor agreement with Scc (ICC ≤ 0.47) and LCS (ICC ≤ 0.37). The correlation between the spacing metrics of the two sampling areas was greater in healthy subjects than in patients with retinal diseases. Conclusions: The Scc and LCS provided interchangeable estimates of cone distance in AO retinal images of healthy subjects but could not be used interchangeably when investigating retinal diseases with significant cell reflectivity loss (≥30%). The DRPD was unreliable for describing cell distance in a human retinal cone mosaic and did not correlate with Scc and LCS. Caution is needed when comparing spacing metrics evaluated in sampling areas of different sizes.