Umberto De Benedetto

Hyperreflective Dots: A New Spectral-Domain Optical Coherence Tomography Entity for Follow-Up and Prognosis in Exudative Age-Related Macular Degeneration

Purpose: Spectral-domain optical coherence tomography (SD-OCT) enables high-resolution analysis of retinal layers and previously unseen hyperreflective dots (HRD). HRD morphological characteristics, evolution, possible origin and prognostic value are discussed. Methods: We conducted a prospective study of 100 patients with exudative age-related macular degeneration (AMD), who were treated and followed up with monthly imaging examinations. Statistical correlations between visual acuity (VA) and pre-/post- treatment HRD characteristics were evaluated. Results: HRD were present in all cases, mainly in the outer retinal layers but also elsewhere. After treatment, HRD regressed in a few days, 1 month (p < 0.04) and 3 months (p < 0.01). Regression was evident in all VA and morphological subsets. Resolution was associated with better final VA (p < 0.001). Conclusions: Presence of initial/recurrent HRD, rapid treatment response and the growing role that early biological inflammatory reaction plays in AMD suggests HRD are activated microglia cells. The correlation between VA and HRD could make HRD a clinical marker for early decisions about treatment and retreatment.

Choroid Thickness Measurement with RTVue Optical Coherence Tomography in Emmetropic Eyes, Mildly Myopic Eyes, and Highly Myopic Eyes:

Purpose. To evaluate choroid thickness (CT) with RTVue spectral domain optical coherence tomography (SD-OCT) and the effect of age and myopia in eyes without posterior complications. Methods. In this multicenter cross-sectional study, all enrolled patients were over age 18 and divided them in 3 groups based on refraction: emmetropia (+1 D to −1 D), mild myopia (–1 D to −6 D), and high myopia (–6 D to −20 D) groups. Horizontal scans through the fovea were acquired with RTVue OCT (Optovue Inc., Fremont, California, USA). Choroid thickness was measured at 500 µm intervals up to 1,500 µm temporal and nasal to the fovea by 2 graders. Mean CT was calculated based on the average of the 7 locations. Statistical analysis was performed to evaluate CT at each location, the effects of age and myopia, and grader agreement. Results. A total 85 eyes of 85 subjects (30 emmetropic, 24 myopic, and 31 high myopic) were enrolled. Excellent grader agreement was observed with an intraclass correlation coefficient (ICC) >0.97. The mean CT was 248.2±78.5 (µm) for emmetropia (age = 58±18), 247.0±85.4 (µm) for myopia (age = 45±20), and 131.5±70.9 (µm) for high myopia (age = 54±13). The mean CT was not significantly different between emmetropia and myopia groups, which were significantly thicker than high myopia group. The overall slope of age-related change for the mean CT was −1.95 µm/y and the effect of age differed among the groups. Conclusions. Choroid thickness can be measured from RTVue OCT images with good reproducibility. Age and high myopia appear to negatively affect CT. The age effect may vary with refraction groups.

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.

Rebound Effect After Intravitreal Dexamethasone Implant for the Treatment of Macular Edema Secondary to Central Retinal Vein Occlusion

AIM To report on the rebound macular edema (ME) effect following dexamethasone implant for the treatment of nonischemic central retinal vein occlusion (CRVO). METHODS Twenty-one patients affected by ME secondary to central retinal vein occlusion (CRVO) underwent an implant of dexamethasone (700 μg) in a compassionate use program. The patients were followed up monthly. The Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), central retinal thickness (CRT) on optical coherence tomography (OCT), and intraocular pressure were registered at monthly intervals. Retreatments were carried out on a pro-re-nata (PRN) basis starting from the third month. RESULTS Both BCVA and CRT improved in all cases. A rebound effect, characterized by a recurrence of ME in excess of the baseline value, occurred in 3 cases (13%) at months 3 and 4. Visual acuity accordingly dropped at the higher CRT values in the 3 cases displaying the rebound effect. Additional treatment with dexamethasone implant led to both a recovery in visual acuity and reduction in CRT. CONCLUSIONS A rebound effect can occur after dexamethasone implant for the treatment of ME related to CRVO, but does not affect functional or anatomical recovery when retreatment is provided. The retreatment rate with dexamethasone implant should be adapted to suit the patients response.

Ranibizumab in the treatment of patients with visual impairment due to diabetic macular edema

Diabetic macular edema is the major cause of visual acuity impairment in diabetic patients. The exact etiopathogenesis is unknown and, currently, grid/focal retinal laser photocoagulation represents the recommended treatment. It has been demonstrated that vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of diabetic macular edema by mediating vascular permeability and accumulation of intracellular and extracellular fluid, and thereby represents an appealing candidate as a therapeutic target for the treatment of diabetic macular edema. The advent of intravitreal anti-VEGF drugs has opened up a new era for the management of diabetic macular edema. At present, three anti-VEGF substances are available for routine clinical use, ie, pegaptanib, ranibizumab, and bevacizumab. The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice. Most of the studies analyzed in this review are prospective, controlled clinical trials that have focused on documenting the therapeutic effect of ranibizumab and its safety, providing encouraging results.

Macular dysfunction is common in both type 1 and type 2 diabetic patients without macular edema

Purpose: To study retinal function in asymptomatic Type 1 and Type 2 diabetic patients with nonproliferative diabetic retinopathy (NPDR) and no clinical signs of diabetic macular edema. Methods: Thirty-six consecutive Type 1 and Type 2 diabetic patients with nonproliferative diabetic retinopathy and no diabetic macular edema and 28 healthy controls underwent a complete ophthalmologic examination, including spectral domain optical coherence tomography and microperimetry. Results: Seventy-one eyes (17 patients with Type 1 and 19 with Type 2 diabetes) were tested, and data from 36 (17 Type 1 and 19 Type 2) eyes were analyzed. Mean best-corrected visual acuity was 0.00 ± 0.01 logMAR and 0.00 ± 0.02 logMAR for Type 1 and Type 2 diabetic patients, respectively (P = 0.075). Mean central foveal thickness was 234.5 ± 13.7 &mgr;m and 256.3 ± 12.7 &mgr;m for Type 1 and Type 2 diabetic patients, respectively (P = 0.04); the central foveal thickness was statistically different compared with the control groups (P = 0.04 and P = 0.01, respectively). Mean retinal sensitivity was 18.9 ± 0.5 dB and 17.7 ± 0.4 dB for Type 1 and Type 2 diabetic patients, respectively; it was statistically different compared with control groups (P < 0.0001 and P < 0.0001, respectively). Conclusion: We demonstrated a significantly reduced sensitivity in both nonproliferative diabetic retinopathy groups without diabetic macular edema compared with healthy controls; this reduction was greater in Type 2 diabetic patients. Central foveal thickness was increased in all diabetic patients compared with healthy controls, despite the absence of diabetic macular edema.

Spectral domain optical coherence tomography findings in patients with retinitis pigmentosa.

Background: To report the morphological macular findings detected by spectral domain optical coherence tomography (SD-OCT) and to determine their prevalence in patients with retinitis pigmentosa (RP). Methods: SD-OCT scans of 176 eyes from 90 patients affected by RP were reviewed. A careful evaluation was carried out on photoreceptor inner/outer segment (IS/OS) junction, external limiting membrane (ELM), inner limiting membrane thickening (ILMT), epiretinal membranes (ERMs), retinal micropseudocysts (MPCs), cystoid macular edema (CME), macular holes (MHs) and choroidal neovascularization (CNV). Results: The photoreceptor IS/OS junction was absent in the foveal region of 24 eyes (13.6%) and disrupted in 84 eyes (47.7%). The ELM was absent in 24 eyes (13.6%), whereas the ILMT was found in 118 eyes (67%). The presence of an ERM was detected in 48 eyes (27.3%). Some sort of vitreomacular alteration (ILMT and/or ERM) was identifiable in a total of 94.3% of eyes with RP. The presence of MPCs was detected in 32 eyes (18.2%). An evident CME was found in 22 eyes (12.5%). We also found MHs in 8 eyes (4.5%) and CNV in 3 eyes (1.7%). Conclusions: Our data indicate that RP is associated with alterations of many retinal layers. In particular, the vitreoretinal interface is affected in 94% of patients, and MPC can be identified in 18% of eyes. SD-OCT may contribute to the understanding of the pathophysiological mechanism involved in RP.

Juxtafoveal choroidal neovascularization associated with retinitis pigmentosa treated with intravitreal bevacizumab.

PURPOSE To describe a case of juxtafoveal choroidal neovascularization (CNV) occurring in a patient affected by retinitis pigmentosa (RP), treated with intravitreal bevacizumab over a 12-month follow-up. METHODS A 66 year-old woman referred to our center for visual acuity deterioration was diagnosed as having classic juxtafoveal CNV associated with RP. The patient was treated with intravitreal bevacizumab, and was regularly monitored every month. RESULTS At the end of the 12-month follow-up, best corrected visual acuity changed from 20/200 to 20/100 in the affected eye. Five intravitreal bevacizumab injections were required to obtain the stabilization of the CNV. CONCLUSIONS Intravitreal bevacizumab is effective in producing juxtafoveal CNV stabilization and visual acuity improvement in a patient affected by RP, over a 12-month follow-up. Future studies are required to ascertain the best therapeutic approach for CNV complicating RP.

Macular micropseudocysts in early stages of diabetic retinopathy.

Purpose: To identify by noninvasive means early retinal abnormalities that may predict diabetic macular edema. Methods: The authors analyzed retrospectively data from consecutive patients with Type 1 (n = 16) or Type 2 (n = 23) diabetes who presented for routine follow-up of early retinopathy, had no clinical signs or symptoms of diabetic macular edema, and were evaluated with spectral-domain optical coherence tomography. Age- and gender-matched nondiabetic subjects provided normative data. Results: Spectral-domain optical coherence tomography revealed in the macular region of diabetic patients small hyporeflective areas (median diameter, 55 μm) contained within discrete retinal layers that we named micropseudocysts (MPCs). Micropseudocysts are associated with vascular leakage. The patients showing MPCs had more frequently systemic hypertension and increased central foveal thickness than those without MPCs. The association with increased central foveal thickness was only in the patients with Type 2 diabetes. Conclusion: Macular MPCs in patients with mild diabetic retinopathy appear to reflect leakage and can precede macular thickening. The association of MPCs with increased central foveal thickness in patients with Type 2 diabetes, but not in patients with Type 1 diabetes, points to a greater tendency to retinal fluid accumulation in patients with Type 2 diabetes. Studies in larger cohorts will determine the usefulness of MPCs in strategies to abort diabetic macular edema.

Intravitreal bevacizumab for juxtafoveal choroidal neovascularization secondary to multifocal choroiditis

Purpose: To assess the effects of intravitreal bevacizumab injections in the treatment of juxtafoveal choroidal neovascularization associated with multifocal choroiditis. Methods: Prospective interventional case series. Fourteen patients (14 eyes) affected by juxtafoveal choroidal neovascularization secondary to multifocal choroiditis were examined. All patients underwent a complete ophthalmologic examination, including measurement of best-corrected visual acuity using Early Treatment Diabetic Retinopathy Study charts, optical coherence tomography, and fluorescein angiography. The protocol treatment included a first injection, followed by repeated intravitreal bevacizumab injections over a 12-month follow-up period on the basis of optical coherence tomography parameters and angiographic features. Results: Mean best-corrected visual acuity changed from 0.41 logarithm of the minimum angle of resolution (approximately corresponding to 20/51 Snellen equivalent), at baseline, to 0.16 ± 0.13 logarithm of the minimum angle of resolution (approximately corresponding to 20/28 Snellen equivalent), at the 12-month examination (P < 0.002). A functional improvement of at least 3 Early Treatment Diabetic Retinopathy Study lines was achieved by 6 eyes (43%) at the 12-month examination. Mean central macular thickness at baseline was 318 &mgr;m, reducing to 239 &mgr;m at the 12-month examination (P < 0.001). No eye showed choroidal neovascularization extension to the fovea. Conclusion: Intravitreal bevacizumab is a beneficial treatment for juxtafoveal choroidal neovascularization associated with multifocal choroiditis. Further studies are warranted to confirm these preliminary results.