Riccardo Sacconi

Optical coherence tomographic hyperreflective foci in early stages of diabetic retinopathy

Purpose: To analyze the presence of hyperreflective foci in Type 1 and Type 2 diabetic patients, separately, without clinically significant diabetic macular edema and visual impairment. Methods: Noninvasive, observational prospective study. Seventeen and 19 consecutive Type 1 and Type 2 diabetic patients (33 and 38 eyes), respectively, were recruited. All patients had no clinically significant diabetic macular edema or visual impairment. Two age- and sex-matched control groups were also included. Patients underwent an ophthalmologic examination including spectral domain optical coherence tomography. Hyperreflective foci were counted considering horizontal B-scan passing through the fovea. Results: On spectral domain optical coherence tomography, patients affected by Type 1 and Type 2 diabetes had a mean of 7.5 ± 4.6 and 9.9 ± 4.5 hyperreflective foci, respectively. Subjects of control groups had a mean of 0.9 ± 0.8 and 1.7 ± 1.5 hyperreflective foci, respectively. Hyperreflective foci amount was statistically different between Type 1 and Type 2 diabetic groups (P = 0.032) and significantly higher in diabetic patients than in controls (P < 0.001). Hyperreflective foci amount was significantly higher in diabetic patients with a poor quality glycometabolic control (P < 0.001 and P = 0.016) or affected by hypertension (P = 0.008). Conclusion: We reported the presence of hyperreflective foci in diabetic patients without diabetic macular edema and visual impairment. This spectral domain optical coherence tomography finding might be a useful marker for the diagnosis and the follow-up in the early stage of diabetic retinopathy.

Optical Coherence Tomography Angiography Macular and Peripapillary Vessel Perfusion Density in Healthy Subjects, Glaucoma Suspects, and Glaucoma Patients

Purpose To evaluate macular and peripapillary vessel perfusion density (VD) in glaucoma suspects (GS) and glaucoma patients; to correlate ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses with macular and peripapillary VD; and to evaluate the diagnostic accuracy of the structural and vascular parameters. Methods A consecutive series of GS, glaucoma patients, and healthy subjects was prospectively recruited from July 1, 2016, to January 31, 2017. All subjects underwent standard automated perimetry, spectral-domain optical coherence tomography (OCT), and 6 × 6-mm optical coherence tomography angiography (OCT-A) centered on the fovea and optic nerve. Results Forty controls, 40 GS, and 40 glaucoma patients were enrolled. Peripapillary RNFL, GCIPL, and macular RNFL thicknesses significantly decreased in the glaucoma group compared to controls and GS (P < 0.01). Peripapillary VD in average and in the superior and inferior quadrants decreased in the glaucoma group (P ≤ 0.001); conversely, macular VD was not statistically different across groups (P > 0.05). At the peripapillary area, a correlation between RNFL thickness and VD was found; conversely, no statistically significant correlation was found between GCIPL thicknesses and macular VD (all P > 0.05) in all groups. Peripapillary RNFL and GCIPL showed higher diagnostic capacity compared to peripapillary and macular VDs. Conclusions Structural damage is evident both in the peripapillary and in macular areas. Vascular damage seems to be less prominent, as it was seen only for the glaucoma group and at the radial peripapillary plexus. Diagnostic abilities are excellent for structural variables, less so but still good for peripapillary VD, and poor for macular VD.

Fundus Autofluorescence Changes After Ranibizumab Treatment for Subfoveal Choroidal Neovascularization Secondary to Pathologic Myopia

PURPOSE To describe fundus autofluorescence (FAF) patterns of myopic choroidal neovascularization (CNV) treated with intravitreal ranibizumab and their correlation with visual acuity. DESIGN Prospective interventional case series. METHODS Twenty-seven eyes (27 patients) affected by myopic CNV were enrolled from January 2011 to January 2013. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) determination and fundus autofluorescence (FAF). The patients underwent ranibizumab injections following a pro re nata treatment regimen. The main outcome measure was the identification of the FAF patterns of myopic CNV over a 12-month follow-up. The secondary outcome was the correlation of the FAF patterns with the BCVA. RESULTS At baseline 17 eyes (63%) showed a hyperautofluorescent pattern and 10 eyes (37%) a patchy pattern. BCVA changed from 0.48 ± 0.23 (logMAR) to 0.30 ± 0.32 at the 12-month examination (P = .027) in the hyper-FAF subgroup. In the subgroup showing the patchy pattern, the BCVA declined slightly from 0.51 ± 0.27 to 0.56 ± 0.37 (P = .53). The 14 eyes preserving the hyper-FAF pattern during the follow-up had a final BCVA of 0.20 ± 0.17, whereas the 9 eyes maintaining the patchy pattern showed a final BCVA of 0.60 ± 0.37 (P = .002). The atrophic area of the retinal pigment epithelium assessed on the basis of FAF increased from 1.27 ± 2.80 mm(2) to 1.83 ± 3.74 mm(2) at the 12-month examination (P = .016). The mean atrophic area increased by 0.37 mm(2) in the hyper-FAF subgroup and by 0.90 mm(2) in the patchy FAF subgroup. CONCLUSIONS Two main patterns were identified on FAF in myopic CNV and were related to the prognostic evolution, the hyperautofluorescent CNV being associated with a greater visual gain and fewer atrophic changes over a 12-month follow-up.

Ultra-wide-field fluorescein angiography in diabetic retinopathy: A narrative review

Fluorescein angiography (FA) is a useful examination in patients suffering from diabetic retinopathy (DR). Traditional angiograms explore 30°-50° of the retina at once; however, visualization of peripheral retina is fundamental in order to assess nonperfused areas, vascular leakage, microvascular abnormalities, and neovascularizations. In order to expand the field of view, wide-field and ultra-wide-field imaging has been developed allowing to image up to 200° of retinal surface in one single shot. The aim of this narrative review was to provide an overview of the role of the most recent technique of ultra-wide-field fluorescein angiography in DR.

Recent advances in the management of dry age-related macular degeneration: A review

Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy. This review focuses on the management of d-AMD and especially on current data about potential targets for therapies evaluated in clinical trials. Numerous examinations are available in clinics to monitor morphological changes in the retina, RPE and choroid of d-AMD patients. Fundus autofluorescence and optical coherence tomography (OCT) are considered the most useful tools in the diagnosis and follow-up of d-AMD alterations, including the monitoring of atrophy area progression. Instead, OCT-angiography is a novel imaging tool that may add further information in patients affected by d-AMD. Several pathways, including oxidative stress, deposits of lipofuscin, chronic inflammation and choroidal blood flow insufficiency, seem to play an important role in the pathogenesis of d-AMD and represent possible targets for new therapies. A great number of treatments for d-AMD are under investigation with promising results in preliminary studies. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity. Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation.

CHOROIDAL THICKNESS IN BEST VITELLIFORM MACULAR DYSTROPHY.

Purpose: To assess the changes in choroidal thickness in different stages of Best vitelliform macular dystrophy (VMD). Methods: Thirty-four patients affected by VMD were prospectively enrolled and underwent a complete ophthalmologic examination, including best-corrected visual acuity measurement, biomicroscopic examination, and spectral domain optical coherence tomography. The Gass classification was used in defining the stages of VMD. Twenty healthy subjects served as the control group. Main outcome measures were the identification of choroidal changes in different stages of VMD and detection of a correlation between choroidal thickness and best-corrected visual acuity. Results: No significant difference was found in the subfoveal choroidal thickness (SFCT) between eyes displaying Stage 1 and the control group (P = 0.181). Stages 2 and 3 showed an increased SFCT (320.4 and 319.1 &mgr;m, respectively) compared with that of control patients (P < 0.001 and P = 0.004, respectively). Stage 4 had a significantly inferior SFCT compared with Stages 2 and 3 (P = 0.007 and P = 0.025, respectively) but no significant difference was found between Stage 4 and control patients (P = 0.733). The Stage 5 group displayed a significant decrease in SFCT compared with that of the control group (181.3 &mgr;m and 238.4 &mgr;m, respectively, P = 0.002). Analyzing the association between SFCT and best-corrected visual acuity in patients affected by clinical VMD (Stages 2–5), the authors found that the best-corrected visual acuity decreased as the choroid thinned (P = 0.004). Conclusion: Choroidal thickness varies according to the stage of VMD, being higher in the vitelliform stage and thinner in the atrophic/cicatricial stage. Long-term studies are warranted to provide a more precise evaluation of the morphofunctional alterations in the different stages of VMD.

Outcome of 110 Basal Cell Carcinomas of the Eyelid Treated with Frozen Section–Controlled Excision: Mean Follow-up over 5 Years:

Purpose To analyze the outcome and risk factors of recurrence in patients with basal cell carcinomas (BCCs) of the eyelid treated by en face frozen section–controlled (FSC) excision with a mean follow-up over 5 years. Methods This was a retrospective series of 108 patients with 110 biopsy-proven eyelid BCCs. All lesions were excised with 2 mm margins clinically free from neoplasia at clinical examination. For each tumor, en face frozen section examination of surgical margins was employed for the histologic confirmation before the reconstruction. Subsequently, all margins were submitted for permanent paraffin sections. Results Of 110 malignancies, 80.9% represented primary carcinomas and 19.1% secondary ones. The overall recurrence rate was 1.8%, with a mean follow-up of 72.4 months (range 30–167). The mean time between the excision of the lesion and the diagnosis of the recurrence was 24 months (range 20–28). No recurrences were observed in 62 tumors followed up for at least 5 years. Secondary BCCs were associated with a higher recurrence rate compared with primary BCCs (4.8% and 1.1%, respectively, p = 0.262). Conclusions The FSC excision of eyelid BCCs yields recurrence rates comparable to those of Mohs micrographic surgery at 5-year follow-up. Intraoperative microscopic margin control improves the cure rate of eyelid BCCs, and FSC excision with small margins (2 mm) clinically free from neoplasia is associated with easier reconstruction and better cosmetic and functional outcomes.

Dexamethasone Implants in Diabetic Macular Edema Patients with High Visual Acuity

Purpose: To evaluate the effects of intravitreal dexamethasone (DEX) implants in patients affected by diabetic macular edema (DME) with high best-corrected visual acuity (BCVA) and contraindications to therapy with anti-vascular endothelial growth factor over a 12-month follow-up. Methods: In this interventional nonrandomized clinical study, 14 consecutive patients (14 eyes) affected by DME with a BCVA of 0.3 LogMAR or better were prospectively enrolled. All patients were treated with a sustained-release 700-μg DEX implant at baseline, revaluated every 6 weeks, and retreated on a pro re nata basis. Primary outcomes included changes in BCVA and central macular thickness (CMT). Secondary outcomes included number of implants, average period between injections, and incidence of side effects. Results: At the 12-month examination, a significant improvement in mean BCVA was noted compared to baseline (from 0.25 ± 0.05 to 0.10 ± 0.07 LogMAR; p < 0.001); CMT decreased from 484 ± 127 to 311 ± 51 μm (p < 0.001). No differences in BCVA and CMT improvements were found between treatment- naïve patients and previously treated patients (p = 0.768 and 0.119, respectively). The mean number of implants was 1.71 ± 0.61 (range, 1-3). The mean period between the first and the second implant was 6.1 ± 1.6 months. Conclusions: The DEX implant on a pro re nata basis can be considered a beneficial approach for DME patients with high BCVA over a 12-month follow-up; functional and anatomical outcome of the patients significantly improved with few injections and a good safety profile.

Optical coherence tomography angiography in the evaluation of geographic atrophy area extension

Purpose To investigate the application of optical coherence tomography angiography (OCT-A) in evaluation of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods Patients with GA were prospectively enrolled and studied with blue fundus autofluorescence (FAF), en face structural OCT, and OCT-A. OCT-A images were acquired using a slab of whole choroid, whereas en face structural OCT images were obtained at the ellipsoid zone (EZ), at the choroidal (CH) level, and at the scleral (SC) level. Three readers independently measured the GA extension areas and evaluated the foveal sparing in each examination. Intraobserver/interobserver agreements and agreement between each couple of imaging techniques were assessed. Results A total of 47 eyes (26 patients, mean age 76 ± 7 years) with GA (mean area using FAF: 8.77 ± 5.00 mm2) were included. Intraobserver and interobserver agreement was excellent for all imaging techniques (intraclass correlation coefficient [ICC] > 0.985), even if en face EZ structural OCT revealed the poorest quality agreement limits. Considering the analysis between each couple of imaging techniques, ICC was excellent between OCT-A compared with FAF (ICC: 0.995), followed by en face structural OCT at CH level (ICC: 0.992), at SC level (ICC: 0.986), and at EZ level (ICC: 0.973). No differences were detected between multifocal and monofocal GA lesions. Considering the evaluation of foveal involvement, lower agreements were disclosed between FAF and all other imaging techniques. Conclusions OCT-A is a reliable technique for easily visualizing and quantifying GA with the advantages, compared to current imaging techniques, of offering together both structural and blood flow information regarding retinal and choroidal layers and excluding choroidal neovascularization.

Choroidal Round Hyporeflectivities in Geographic Atrophy.

Purpose In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A). Methods Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed. Results Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01). Conclusions Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow.