OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ASSESSMENT OF THE DIABETIC MACULA: A Comparison Study Among Different Algorithms.

PURPOSE: To assess the impact of histogram adjustments and binarization thresholding selection on quantitative measurements of diabetic macular ischemia using optical coherence tomography angiography (OCTA). METHODS: Patients with diabetic retinopathy (DR) who had swept-source OCTA imaging obtained were enrolled. An additional group of 15 healthy control subjects was included for comparison. Previously used brightness/contrast changes and binarization thresholds were applied to original OCTA images to obtain and compare different binarized images. Qualitative and quantitative comparisons were performed. RESULTS: Thirty patients with DR (30 eyes) were included in the analysis. Fifteen eyes displayed the presence of diabetic macular edema. Qualitative grading revealed that binarized images obtained using a global threshold had better quality compared with local or multistep thresholds. The "median" filter was most frequently graded as the histogram adjustment resulting in binarized images with best quality. In the quantitative analysis, local thresholds tended to generate higher values of measured metrics. Differences in OCTA metrics between global and local thresholds were associated with presence of diabetic macular edema and signal strength index value. In the comparison between healthy and DR eyes, differences in OCTA metrics were significantly affected by binarization threshold selection. CONCLUSION: Quantitative OCTA parameters may be significantly influenced by strategies to quantify macular perfusion. Image quality and presence of macular edema can significantly impact OCTA-derived quantitative vascular measurements and differences between global and local binarization thresholds. These findings highlight the importance of consistent strategies to reliably generate quantitative OCTA metrics in patients with DR.

Microvasculature Changes of Myopic Choroidal Neovascularization and the Predictive Value of Feeder Vessel Disappearance after Ranibizumab Treatment Revealed Using Optical Coherence Tomography Angiography.

AIM: To investigate vascular changes of myopic choroidal neovascularization (mCNV) after ranibizumab treatment using optical coherence tomography-angiography (OCTA). METHODS: Consecutive subjects with a diagnosis of mCNV were included. Patients underwent intravitreal injection of ranibizumab treatment with a 6-month follow-up. All patients underwent a complete ophthalmological examination and OCTA evaluation. The 3 × 3 OCTA en face images were analyzed for the absence/presence of mCNV, CNV area, and CNV network morphology. In particular, the morphology of the mCNV was analyzed in order to detect the presence/absence of feeder vessels. RESULTS: Eleven subjects were evaluated. At baseline, the mCNV was identified in all cases on OCTA. At 6 months, the mean mCNV area was not statically significantly reduced in comparison with baseline values (p > 0.05), while the morphologic analysis revealed a complete disappearance of the feeder vessel in 6 eyes. The subgroup analysis of these latter showed that the CNV area was significantly reduced, visual acuity had improved, and only one intravitreal injection was administrated over the entire follow-up period. CONCLUSIONS: OCTA allowed the detection of qualitative and quantitative vascular changes in mCNV. The disappearance of the feeder vessel was associated with better anatomical as well as functional outcomes at the last follow-up visit.

Treatment of Diabetic Macular Edema with Multiple Dexamethasone Intravitreal Implants: Evidence from Real-Life Experience.

OBJECTIVE: To gain information about multiple dexamethasone intravitreal implant (DEX-I) injections in diabetic macular edema (DME) eyes in real-life clinical settings. METHODS: Patients with DME treated with multiple (≥5) DEX-I injections between January 1, 2014, and December 31, 2018, were retrospectively enrolled regardless of previous treatment with anti-VEGF agents. All patients were evaluated with best-corrected visual acuity (BCVA) in logMAR, ocular fundus, and spectral domain optical coherence tomography (SD-OCT) at baseline and at 3 months after the last DEX-I injection. Multiple DEX-I injections were administered when necessary in case of DME recurrence. Main efficacy measures were changes in BCVA and central retinal thickness (CRT) from baseline to 3 months after the last DEX-I injection; main secondary measures were an increase in intraocular pressure (IOP), the need for cataract surgery, endophthalmitis, and vitreous hemorrhage. RESULTS: Seventeen patients (18 eyes) with DME and mean age (± SD) of 54.3 ± 8.16 years were treated with DEX-I injections between 2014 and 2018. The majority of eyes (77.8%) had been treated with a mean of 6.3 ± 3.2 anti-VEGF agents before switching to DEX-I. During a mean follow-up period of 37.6 months and after a mean number of 5.9 DEX-I injections, visual acuity improved or stabilized in 77.8% of all eyes, accompanied by a significant reduction in CRT. An increase in IOP was recorded in 38.8% of all patients, while a surgical procedure was needed for cataract in 73.3% of all phakic patients. CONCLUSIONS: In this real-life experience in Italy, multiple DEX-I treatments showed good efficacy with no new safety concerns. The follow-up duration of >3 years and a greater number of DEX-I intravitreal injections compared to other observations confirm the positive balance between risks and benefits of DEX-I in the long term.

Single Retinal Layer Evaluation in Patients with Type 1 Diabetes with No or Early Signs of Diabetic Retinopathy: The First Hint of Neurovascular Crosstalk Damage between Neurons and Capillaries?

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.

Prospective evaluation of morphological and functional changes after repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion.

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.

Photodynamic therapy in subfoveal and juxtafoveal myopic choroidal neovascularization: a 10-year retrospective analysis.

The aim of this study was to evaluate and compare the effects of photodynamic therapy (PDT) in eyes with subfoveal and juxtafoveal choroidal neovascularization (CNV) secondary to pathological myopia. The study was a single-center, 10-year analysis on 19 eyes. Patients underwent best-corrected visual acuity (BCVA) measurement, slit-lamp examination, ophthalmoscopy and fluorescein angiography. Eyes with subfoveal CNV (7 eyes, 37%) progressively worsened during the 10-year follow-up from 0.68 ± 0.26 to 0.80 ± 0.47 logMAR, while in the eyes with juxtafoveal CNV (12 eyes, 63%) BCVA improved from 0.59 ± 0.42 to 0.33 ± 0.27 logMAR. Prevalence and extension of chorioretinal atrophy (CRA) were greater in eyes with subfoveal compared with juxtafoveal CNV (84 vs. 66%, respectively) and enlargement (10.05 ± 6.7 vs. 3.53 ± 4.7 mm(2), respectively). Our results confirm the limited long-term effectiveness of PDT in myopic subfoveal CNV. Satisfactory results can be achieved in juxtafoveal CNV with a better visual outcome and a minor CRA extension.

Exploring the morphological and functional retinal changes after dexamethasone intravitreal implant (Ozurdex®) in macular edema due to retinal vein occlusion.

PURPOSE: To explore functional and morphological retinal changes 6 months after dexamethasone intravitreal implant (DEX implant) for the treatment of macular edema due to central or branch retinal vein occlusion (CRVO, BRVO). PROCEDURES: In this prospective interventional case series patients underwent a complete ophthalmological examination at baseline and monthly, including best-corrected visual acuity (BCVA), spectral domain-optical coherence tomography and microperimetry. Fluorescein angiography was performed at baseline and at 4 months. All patients were treated with a DEX implant and retreated according to predefined criteria starting from month 4. RESULTS: Sixteen patients (mean age 66 ± 13 years, 14 CRVO, 2 BRVO) were included. At 6 months mean retinal sensitivity improved from 9.7 ± 4.6 to 13.6 ± 5.4 dB (p < 0.0001) while mean BCVA improved from 52.4 ± 16.2 to 66.1 ± 16.6 (p < 0.0001). Mean central retinal thickness decreased from 708.3 ± 151.01 to 362.7 ± 177.4 µm (p < 0.0001); 56.2% of eyes were retreated at month 4. CONCLUSIONS: At 6 months DEX implant led to a significant improvement in retinal sensitivity and visual acuity associated with a reduction of retinal thickness in patients with macular edema due to retinal vein occlusion.

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

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

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

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

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.

Bietti crystalline dystrophy: a morpho-functional evaluation.

We report the clinical findings and macular function of a patient with Bietti crystalline dystrophy. A 39-year-old woman reported visual loss in both eyes and nyctalopia. A complete ophthalmological evaluation, retromode imaging, SD-OCT acquisition, MP1 microperimetry, and multifocal electroretinogram (mfERG) were performed. Microcrystalline deposits in the cornea and the retina with retinal pigment epithelial atrophy were observed. Retromode imaging revealed visualization of normal large choroidal vessels, cystoid macular edema, and small defined glistening lesions. SD-OCT showed changes in the outer retina with numerous microcrystalline deposits. Microperimetry showed an absolute scotoma involving the perimacular area but sparing of the fovea. In both eyes, mfERG analysis suggests a dysfunction of pre-ganglionic retinal elements detectable in the 20 central retinal degrees. The genetic characterization showed an homozygous mutation c.772C > T[p.Leu258Phe] in exon 6. Retromode imaging and SD-OCT were useful tools to determine the extent and the localization of the crystals. Microperimetry should allow evaluation of the progression of the macular changes.

Structural and optical coherence tomography angiography in myopic choroidal neovascularization: Agreement with conventional fluorescein angiography.

PURPOSE: To evaluate the agreement between fluorescein angiography and structural optical coherence tomography in diagnosing and monitoring the activity of myopic choroidal neovascularization and to provide a comparative analysis with optical coherence tomography angiography. METHODS: Thirteen patients with active myopic choroidal neovascularization were prospectively enrolled. At the baseline, 2-month, and 6-month visits, each patient underwent a complete ophthalmological examination, including best-corrected visual acuity assessment, fundus examination, fluorescein angiography, and optical coherence tomography with structural and angiographic assessment. Sensitivity and specificity for all optical coherence tomography parameters were evaluated taking fluorescein angiography as the reference examination. RESULTS: At the baseline, fluorescein angiography confirmed myopic choroidal neovascularization leakage in all patients. Structural optical coherence tomography demonstrated intraretinal or subretinal fluid in 61% of cases, fuzzy borders and absence of external limiting membrane visibility in 84% of cases, and subretinal hyperreflective exudation in 53% of cases. Sensitivity to the presence of retinal fluid and subretinal hyperreflective exudation was lower than sensitivity to fuzzy borders and external limiting membrane visibility, which reached 84%. During ranibizumab therapy, external limiting membrane visibility showed a higher sensitivity (100%) compared with fuzzy borders and subretinal hyperreflective exudation (66.6%) while displaying an equal specificity of 100%. At baseline and final visit, sensitivity increased to 100% when all structural optical coherence tomography parameters were pooled. Optical coherence tomography angiography detected myopic choroidal neovascularization at baseline, 2-month, and 6-month visits in 92%, 76%, and 76% of cases, respectively. CONCLUSION: The study confirms that the new indicators of myopic choroidal neovascularization activity are more reliable than the presence or absence of retinal fluid. Optical coherence tomography angiography identified myopic choroidal neovascularization in most patients in the diagnostic phase and during treatment monitoring and could be considered as an alternative to fluorescein angiography in selected patients.

Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 36-Month Pilot Study Evaluating Macular Electrophysiological Changes.

INTRODUCTION: Our aim was to evaluate the effects of 36 months of treatment with citicoline and vitamin B12 eye drops on macular function in patients with type 1 diabetes (DM1) with mild signs of non-proliferative diabetic retinopathy (NPDR). METHODS: A prospective, randomized, interventional, monocentric, double-masked study was conducted. Twenty patients with DM1 were enrolled and randomly divided into two groups: the DC group (10 patients; mean age ± standard deviation 46.86 ± 8.78 years) in which one eye of each patient was treated with citicoline and vitamin B12 eye drops (OMK2®, Omikron Italia srl, Italy, one drop thrice daily) for a period of 36 months; the DP group (10 patients; mean age ± standard deviation 47.89 ± 7.74 years) in which one eye of each patient was treated with placebo (eye drops containing hypromellose 0.3%, one drop thrice daily) for a period of 36 months. A total of 18 eyes (10 from the DP and 8 from the DC group, respectively) completed the study. In both groups, multifocal electroretinogram (mfERG) recordings were assessed at baseline and after 36 months. In mfERG analysis, the N1-P1 response amplitude density (RAD) evaluated in the 0-2.5° (ring 1), in the 2.5-5° (ring 2), in the 5-10° (ring 3), and in the 0-10° (ring 1 + ring 2 + ring 3) were considered. RESULTS: With respect to baseline, after 36 months of follow-up, the mfERG RADs recorded in R1, R2, R3, and R1 + R2 + R3 were significantly increased (i.e., R1 + R2 + R3 RAD from 21.552 ± 2.522 nV/degree2 at baseline to 26.912 ± 2.850 nV/degree2 at 36 months) in DC eyes, whereas in DP eyes they were significantly reduced (i.e., R1 + R2 + R3 RAD from 21.033 ± 3.574 nV/degree2 at baseline to 16.151 ± 3.571 nV/degree2 at 36 months). CONCLUSIONS: This study indicates that patients with NPDR treated with citicoline and vitamin B12 eye drops for a 36-month period achieved an improvement of the macular bioelectrical responses detectable by mfERG recordings. By contrast, during the same period of follow-up, patients with NPDR treated with placebo showed a worsening of the macular function.

Effectiveness of a Hydrophilic Curcumin-Based Formulation in Coadjuvating the Therapeutic Effect of Intravitreal Dexamethasone in Subjects With Diabetic Macular Edema.

Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME). Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety. Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T0 to the 6 months' evaluation was significant (p = 0.00). The mean CRT result was significantly different at month 4 (p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls. Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings.

Intravitreal dexamethasone implant one month before versus concomitant with cataract surgery in patients with diabetic macular oedema: the dexcat study.

PURPOSE: To report clinical outcomes of two different timings of intravitreal dexamethasone (DEX) implant administration for prevention of diabetic macular oedema (DME) worsening following cataract surgery. METHODS: This multicentre, retrospective study included patients with DME who received an intravitreal DEX implant 1 month before cataract surgery, 'precataract DEX' group, or at the time of cataract surgery, 'concomitant treatments' group. Inclusion criteria were a follow-up ≥3 months and ophthalmological examination with optical coherence tomography (OCT) imaging at baseline (cataract surgery) and throughout follow-up. Anatomical improvement was considered to be a decrease in OCT central subfield (CSF) thickness ≥20% compared to baseline. The primary outcomes were anatomical and functional results at 3 months. RESULTS: Two hundred twenty-one patients were included: 136 in the 'precataract DEX' group and 85 in the 'concomitant treatments' group. At 3 months, a reduction of CSF thickness ≥ 20% was found in 7.3% of eyes in the 'precataract DEX group' and in 83.7% of eyes in the 'concomitant treatments' group (p < 0.001), with mean CSF thickness lower in the latter group (371 ± 52 µm versus 325 ± 57 µm, p < 0.001). At 3 months, mean best-corrected visual acuity had improved from baseline in both groups (p < 0.001), with no difference between groups (p = 0. 20). No serious systemic adverse events were reported. CONCLUSION: Both approaches prevented a worsening of DME, showing a comparable visual outcome. Dexamethasone (DEX) implant given at the same time as cataract surgery provided a better anatomical outcome.

Microvascular impairment as a biomarker of diabetic retinopathy progression in the long-term follow up in type 1 diabetes.

This study aimed to explore differences in vascular and structural parameters using optical coherence tomography angiography in patients with type 1 diabetes (DM1) with mild signs of diabetic retinopathy (DR) over a two-year follow-up period. Parafoveal vessel density (PVD) and foveal avascular zone (FAZ) area were analyzed. The thickness of three predefined retinal slabs was measured, including the inner limiting membrane (ILM)-inner plexiform layer (IPL), IPL-inner nuclear layer (INL), and the IPL-outer nuclear layer (ONL). Twenty-two patients with DM1 and 21 controls were included. There was no significant difference in the FAZ area, perimeter and acircularity index between cohorts over time. Baseline superficial capillary plexus PVD was approximately 10% lower in patients with diabetes than in controls (p = 0.001), and was 12% lower at 2 years (p = 0.002). There was no difference in the annual linear trend between the groups (- 0.5% in diabetics vs. controls, p = 0.736). Baseline deep capillary plexus (DCP) PVD was slightly lower in diabetics than in controls (- 4.4%, p = 0.047) and the difference increased at 2 years (- 12.6%, p < 0.001). The annual linear trend was - 2.7% in diabetic patients compared to controls (p = 0.009). In addition, the PVD of the DCP and the intermediate capillary plexus (ICP) were evaluated separately. Regarding the DCP PVD, no statistically significant difference at any time points in diabetic patients compared to controls and no statistically significant difference in the linear trend was found (p > 0.1). Conversely, no difference was recorded for parafoveal ICP density at individual time points (p > 0.1), but a statistically significant difference in the linear trend over time in diabetic patients compared to controls was recoded (- 3.2% per year, p = 0.001). Despite the apparent intergroup differences at baseline in structural OCT parameters, the differences including ILM-IPL (p = 0.273), IPL-INL (p = 0.708), and IPL-ONL (p = 0.054) were modest and not statistically significant with time. Therefore, the microvascular change of the deeper vessels might be a robust biomarker to evaluate the clinical progression of DR in DM1.

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.

Macular Functional and Morphological Changes in Intermediate Age-Related Maculopathy.

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.