M1 patients with no or mild signs of retinopathy have reduced parafoveal vessel density in the DCP on OCTA when compared to non-diabetic controls. These OCTA findings suggest that parafoveal capillary nonperfusion is an early process in DM1-related retinal changes and occurs initially at the level of the DCP. Further investigation is needed to understand the prognostic role of these vascular changes.

AimsRecent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified.MethodsTo explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants (C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal (N)/temporal (T)/superior (S)/inferior (I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring.ResultsThe difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant (F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (−3.9 for noDR and −4.9 for NPDR), without any relevant difference between them (−1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32–15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33–15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index (r = −0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action −1, −2, −4 h (r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL (r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides resulted both independent predictors of increased INL thickness. No correlation was found with HbA1c.ConclusionsEarly structural damage of neuroretina in persons with Type 1 DM patients is related to glucose fluctuations. GV should be addressed, even in the presence of a good metabolic control.

Introduction: This study aimed to evaluate the effect of treatment with eye drops containing citicoline and vitamin B 12 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 B 12 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 B 12 eye drops (OMK2 Ò , 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 B 12 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.

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Purpose: To analyze the retinal-choroidal changes in type 1 diabetes mellitus (DM1) patients with no or early signs of diabetic retinopathy (DR). Methods: Seventy-six eyes of 38 DM1 patients and 26 control eyes were included. Nine individual retinal layer thickness measurements were obtained using the spectral domain-optical coherence tomography automated segmentation algorithm. Results: The retinal nerve fiber layer was slightly thinner in all explored quadrants, even if the reduction was not significant in DM1 eyes versus control eyes. The inner nuclear layer (INL) thickness was thicker in all DM1 eyes versus control eyes in all quadrants (p < 0.050). Analyses adjusting for inner retinal thickness in all sectors confirmed INL thickening by about 4%, and also found a significant thinning of the ganglion cell layer (GCL) by about 3.5% in all DM1 subjects versus controls (p < 0.050). Conclusion: DM1 patients with no or early signs of DR present retinal changes particularly at the INL and GCL that might be correlated to initial findings of neurodegeneration.

BackgroundTo evaluate the effects of Macuprev® supplementation on macular function and structure in intermediate age-related macular degeneration (AMD) along 6 months of follow-up.MethodsIn this double-blind, monocentric, randomized, and prospective study, 30 patients with intermediate AMD were enrolled and randomly divided into two age-similar groups: 15 patients (AMD-M group; mean age 68.50 ± 8.79 years) received 6-month oral daily supplementation with Macuprev® (Farmaplus Italia s.r.l., Italy, two tablets/day on an empty stomach, before meals; contained in total lutein 20 mg, zeaxanthin 4 mg, N-acetylcysteine 140 mg, bromelain 2500GDU 80 mg, vitamin D3 800 IU, vitamin B12 18 mg, alpha-lipoic acid 140 mg, rutin 157 mg, vitamin C 160 mg, zinc oxide 16 mg, Vaccinium myrtillus 36% anthocyanosides 90 mg, Ganoderma lucidum 600 mg) and 15 patients (AMD-P group; mean age 70.14 ± 9.87) received two tablets of placebo daily on an empty stomach, before meals. A total of 28 eyes, 14 from each AMD group, completed the study. Multifocal electroretinogram (mfERG) and spectral domain-optical coherence tomography (SD-OCT) were assessed at baseline and after 6 months.ResultsAt 6-month follow-up, AMD-M eyes showed a significant increase of mfERG response amplitude density (RAD) recorded from the central macular areas (ring 1, 0–2.5°; ring 2, 2.5–5°), whereas non-significant changes of retinal and choroidal SD-OCT parameters were found when values were compared to baseline. Non-significant correlations between functional and structural changes were found. In AMD-P eyes, non-significant differences for each mfERG and SD-OCT parameters were observed at 6 months.ConclusionsIn intermediate AMD, Macuprev® supplementation increases the function of the macular pre-ganglionic elements, with no associated retinal and choroidal ultra-structural changes.Trial RegistrationClinicalTrials.gov identifier, NCT03919019.FundingResearch for this study was financially supported by the Italian Ministry of Health and Fondazione Roma. Article processing charges were funded by Farmaplus Italia s.r.l., Italy.

Purpose The purpose of this study was to evaluate macular preganglionic function and to verify its relationship with retinal and choroidal morphology in patients with intermediate age-related macular degeneration (iAMD) patients. Methods All included patients performed multifocal electroretinogram (mfERG) for investigating on macular function from the central 15° of foveal eccentricity, spectral domain optical coherence tomography (SD-OCT) for studying retinal structure, enhanced depth imaging OCT (EDI-OCT) for the measure of choroidal vascularity index (CVI), and OCT-angiography (OCTA) for the evaluation of vessel density (VD) in the superficial and deep capillary plexus, and choriocapillaris (CC) layer. Results Twenty-seven patients with iAMD and 20 age-matched control eyes were analyzed. Significantly ( P < 0.01) delayed and reduced mfERG responses in the central 0 to 2.5°, paracentral 2.5 to 5°, and overall 0 to 5° areas, as well as increased CVI values in both foveal (1 mm centered to the fovea) and fovea + parafovea areas (3 mm centered to the fovea), increased foveal and parafoveal (annular area of 1–3 mm centered to the fovea) retinal pigment epithelium thickness, and volume and parafoveal outer retinal volume were found in iAMD eyes as compared to controls. Moreover, iAMD eyes showed significantly ( P < 0.01) reduced foveal and parafoveal OCTA-VD values in the CC layer when compared to controls. In the iAMD group, not significant ( P > 0.01) correlations were found between morphological and functional parameters. Conclusions Our findings support a dysfunction of photoreceptors and bipolar cells in both foveal and parafoveal areas in the presence of outer retina, CC, and choroidal structural changes, however, not significantly correlated. The observed enlargement of luminal choroidal area (measured by CVI) is possibly compensatory to CC vascular insufficiency.

Aims: To evaluate changes in macular morphology and function after repeated intravitreal dexamethasone implant (Ozurdex®) for macular edema (ME) due to retinal vein occlusion (RVO). Methods: Consecutive treatment-naïve patients with ME secondary to RVO were treated with Ozurdex and followed up to 12 months to evaluate functional and morphological outcomes by means of best-corrected visual acuity (BCVA) and microperimetry and by enhanced depth imaging optical coherence tomography, respectively. Results: Thirty-five eyes of 35 patients were included for the analysis (26 central RVO, 9 branch RVO). During the 12-month study period, 8 of the 35 eyes (23%) underwent 1 intravitreal dexamethasone implant, 13 of the 35 eyes (37%) underwent 2, and 14 of the 35 eyes (40%) underwent 3 intravitreal dexamethasone implants. At 1 month from the 1st intravitreal dexamethasone implant, the mean BCVA, retinal sensitivity and central macular thickness (CMT) significantly improved compared to the baseline values. At 3 months, the mean BCVA improvement was no more significant, while retinal sensitivity further improved and CMT slightly worsened, remaining, however, significantly better than at baseline. At 12 months, those eyes that had undergone 2 retreatments showed a significant improvement of the mean BCVA, mean retinal sensitivity and CMT compared to the baseline values [0.61 ± 0.29 logarithm of the minimum angle of resolution (LogMAR) vs. 0.82 ± 0.33 LogMAR, p = 0.011; 12.94 ± 4.73 dB vs. 10.75 ± 3.27 dB, p = 0.043, and 321 ± 91 µm vs. 735 ± 169 µm, p = 0.001, respectively]. In those eyes that had undergone only 1 retreatment, a significant improvement was recorded only for the CMT (500 ± 224 µm vs. 695 ± 302 µm, p = 0.044). The mean retreatment interval between the 1st and the 2nd injection was 4.5 ± 1.1 months (range 3-7 months), and between the 2nd and the 3rd injection it was 4.1 ± 1 months (range 3-6 months). Conclusions: In eyes with ME secondary to RVO, Ozurdex produces functional benefits as early as 1 month after treatment/retreatment. Current optical coherence tomography and microperimetry findings confirm the concept that, in most cases, the optimum retreatment interval should be <6 months from the 1st injection.