Sterile Corneal Infiltrates following Cataract Surgery: Case Series.

We report a case series of 26 eyes of 26 patients undergoing planned cataract surgery from December 2021 to March 2022, who were diagnosed as having whitish round infiltrates in the surgical corneal incisions. The infiltrates were detected at the first check after 5-8 days from cataract surgery and were located either within the main corneal incision and/or in the smaller incisions. Corneal infiltrates (CIs) were single or multiple, without epithelial defects, and painless. All infiltrates were initially treated with full topical antibiotic coverage, in order to control eventual and serious postsurgical infection. However, at daily checks, the clinical course of CIs suggested a sterile etiology. For this reason, steroidal topical treatment was maintained for a long time with slow tapering until complete remission of the CIs. All infiltrates resolved completely in around 30-40 days. The surgical instruments and the sterilization process were scrutinized. A white amorphous material was found mainly on non-disposable anterior chamber cannulas and on irrigation/aspiration tips. Disposable cannulas were adopted, and machinery for cleaning and sterilization procedures were reviewed, with specific reference to water softener renewal. Thanks to these precautions, CIs never occurred again. Finally, our hypothesis was an immune corneal reaction to amorphous deposit on cannula tips. This case series describes a previously unknown complication of cataract surgery and our experience might be useful for other surgeons.

Outcome of cataract surgery in children affected by malignancies other than retinoblastoma with eye-lens radiation exposure.

PURPOSE: To describe, retrospectively, the visual outcome, feasibility, and safety of cataract surgery in a pediatric population affected by iatrogenic cataract, secondary to systemic oncological treatment for malignancies other than retinoblastoma. METHODS: Young patients, affected by radiation-induced cataract, who were referred to the San Paolo Ophthalmic Center in Padova between 2010 and 2017, were included in the study. All patients had previously received radiotherapy and/or chemotherapy treatment for malignancies, between 2004 and 2013. All medical records of infants who underwent cataract surgery were accurately reviewed. RESULTS: Eighteen eyes out of 11 patients included in the study underwent cataract surgery. The mean age at surgery was 9.7 ± 3.6 years. The interval between tumor diagnosis and cataract development was around 3 years. Mean follow-up after surgery was 15.4 ± 6.3 months. All eyes underwent posterior chamber intraocular lens implantation, posterior capsulotomy, and anterior vitrectomy in one time surgery. No intraoperative complications were shown. Post-operatively, only one eye received laser capsulotomy due to posterior capsule opacification. At the end of follow up, best-corrected visual acuity was 20/20 (LogMAR 0) in all eyes and significantly improved (p < 0.01) compared to baseline. CONCLUSIONS: Iatrogenic-cataract surgery in pediatric oncological patients is a safe and effective way to improve visual acuity. Posterior capsulotomy and anterior vitrectomy at the time of surgery reduce the rate of posterior lens opacification and guarantee an excellent visual acuity in these patients.

Severe retinopathy of prematurity is associated with early post-natal low platelet count.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.

Bilateral Isolated Spherophakia in Two Young East European Siblings: A Case Report.

A 19-year-old Caucasian woman was referred to the emergency room and thereafter to the department of ophthalmology complaining for bilateral decrease of visual acuity and severe pain. A complete ophthalmological evaluation was performed. Best-corrected visual acuity (BCVA) was LogMAR 0.3 in the right eye (RE) and LogMAR 0.5 in the left eye (LE). Intraocular pressure (IOP) was 28 and 38 mm Hg in the RE and LE, respectively. The patient showed a shallow anterior chamber and spherical equivalent refractive error -29.0 diopters (D) in the RE and -30.0 D in the LE. The diagnosis of bilateral angle closure glaucoma, secondary to highly myopic, forward dislocated lens was made, in the setting of spherophakia. The ultra-sound biomicroscopy images confirmed the diagnosis. Clear lens extraction was promptly performed with resolution of ocular hypertension and restoration of BCVA. In view of the frequent systemic association, family members also underwent ophthalmological evaluation. The 13-year-old sibling showed mild myopia and borderline IOP. He was administered topical ß-blockers and observation. Genetic counseling did not reveal mutations usually associated with spherophakia or systemic conditions. This case report highlights the variable spectrum of clinical expression in spherophakia; therefore, ophthalmological treatment should be tailored according to clinical presentation. Systemic evaluation and genetic counseling are also recommended in the suspicion of spherophakia.

Corneal side effects induced by EGFR-inhibitor antibody-drug conjugate ABT-414 in patients with recurrent glioblastoma: a prospective clinical and confocal microscopy study.

BACKGROUND: The aim of this study was to prospectively analyse, for the first time worldwide by in vivo clinical confocal microscopy (CCM), corneal side effects secondary to the use of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in a cohort of patients affected by EGFR-amplified recurrent glioblastoma. METHODS: Each enrolled patient underwent full ophthalmologic examination including in vivo CCM of the cornea. Each patient was examined at baseline and every 2 weeks during treatment as long as patient conditions allowed it. RESULTS: A total of 10 patients were consecutively enrolled. Median follow-up was 5 months. No Common Terminology Criteria for Adverse Events Version 4.0 grade 4 toxicity was documented. Two (20%) grade 3 toxicities were documented at week 8. CCM examination detected in all eyes multiple and diffuse hyperreflective white round spots in the corneal basal epithelial layers (100%), progressive subbasal nerve plexus layer fibres fragmentation followed by full disappearance (100%) and appearance of round cystic structures in the corneal epithelium (100%). All CCM documented side effects reached the peak of prevalence and severity after a median of 3 infusions. After treatment discontinuation, the reversibility of corneal side effects was documented at CCM after a median of 4 weeks. CONCLUSION: ABT-414 toxicity is not only directed to the corneal epithelium, but also to corneal nerves. Side effects are detectable in all treated patients and CCM documents early corneal epithelium and subbasal nerve plexus toxicity, with subsequent progressive restoration after treatment discontinuation. Ocular side effects due to ABT-414 can be manageable.

Final versus referral diagnosis of childhood visual impairment in an Italian tertiary low vision rehabilitation centre.

PURPOSE: To compare the final diagnosis of the causes of low vision in children attending a tertiary rehabilitation centre for visually impaired children versus referral diagnosis. METHODS: Retrospective review of clinical charts of all children referred to the Robert Hollman Foundation, a tertiary centre for visually impaired children, between January 2010 and June 2011. The following clinical data were analysed: entry diagnosis made by the referral ophthalmologist and final diagnosis made at Robert Hollman Foundation based on a complete ophthalmic evaluation. RESULTS: Ninety-two consecutive children (mean age = 2.37 ± 1.98 years, range = 0-9) were included. A referral diagnosis was retrieved in 76 cases (82.6%), including cerebral visual impairment (14.1%), retinopathy of prematurity (14.1%), hereditary retinal diseases (10.9%), nystagmus (8.7%) and other rarer diseases (34.8%). In the remaining 16 children (17.4%), a precise referral diagnosis was unavailable. Final clinical diagnosis made at Robert Hollman Foundation was normal visual function in 8.7%, cerebral visual impairment in 30.4%, retinopathy of prematurity in 10.9%, hereditary retinal disease in 9.8% and other in 40.2%. In 17 cases (18.5%), the diagnosis made at the Robert Hollman Foundation did not confirm the entry diagnosis. Among patients where measurement of visual acuity was possible (84), 66.7% were blind or seriously visual impaired, and the main causes were cerebral visual impairment (32.1%) and retinopathy of prematurity (16.1%). CONCLUSION: The most frequent diseases were cerebral visual impairment, retinopathy of prematurity and hereditary retinal diseases. Approximately one-third of referred children had not a correct diagnosis at baseline. The activity of an ophthalmic tertiary centre is essential to offer a precise diagnosis to visually impaired (sometimes with other deficits) children.

CHANGES OF AQUEOUS HUMOR MÜLLER CELLS' BIOMARKERS IN HUMAN PATIENTS AFFECTED BY DIABETIC MACULAR EDEMA AFTER SUBTHRESHOLD MICROPULSE LASER TREATMENT.

PURPOSE: To evaluate the changes in activity of biomarkers of Mu[Combining Diaeresis]ller cells (MC) in aqueous humor of patients with diabetic macular edema after subthreshold micropulse laser, over 1 year. METHODS: Patients with untreated diabetic macular edema and central retinal thickness ≤ 400 µm were enrolled. Best-corrected visual acuity, full ophthalmic examination, and optical coherence tomography were performed. Subthreshold micropulse laser was applied every 3 months. Glial fibrillary acidic protein and inwardly rectifying potassium channel (Kir 4.1), MC activity markers, and vascular endothelial growth factor were quantified in the aqueous humor collected at baseline and at 1, 3, and 12 months after laser. Changes in the macular thickness and inner nuclear layer thickness, where MC bodies are located, were measured. RESULTS: Ten eyes of 10 patients were included. Best-corrected visual acuity improved at 3 months (P = 0.047) and remained stable. Inner nuclear layer thickness significantly reduced at 12 months (P = 0.012). Glial fibrillary acidic protein, Kir 4.1, and vascular endothelial growth factor decreased at 1 and/or 3 and/or 12 months compared with baseline (P < 0.05). CONCLUSION: Subthreshold micropulse laser improves visual function in diabetic macular edema. Kir 4.1 and glial fibrillary acidic protein decrease and inner nuclear layer thickness reduction demonstrate that subthreshold micropulse laser may restore MC function. Subthreshold micropulse laser also reduces vascular endothelial growth factor concentration. The effect of subthreshold micropulse laser in diabetic macular edema may in part be due to changes of MC metabolic activity.

Uveal Melanoma Biopsy: A Review.

Intraocular tumor diagnosis is based on clinical findings supported by additional imaging tools, such as ultrasound, optical coherence tomography and angiographic techniques, usually without the need for invasive procedures or tissue sampling. Despite improvements in the local treatment of uveal melanoma (UM), the prevention and treatment of the metastatic disease remain unsolved, and nearly 50% of patients develop liver metastasis. The current model suggests that tumor cells have already spread by the time of diagnosis, remaining dormant until there are favorable conditions. Tumor sampling procedures at the time of primary tumor diagnosis/treatment are therefore now commonly performed, usually not to confirm the diagnosis of UM, but to obtain a tissue sample for prognostication, to assess patient's specific metastatic risk. Moreover, several studies are ongoing to identify genes specific to UM tumorigenesis, leading to several potential targeted therapeutic strategies. Genetic information can also influence the surveillance timing and metastatic screening type of patients affected by UM. In spite of the widespread use of biopsies in general surgical practice, in ophthalmic oncology the indications and contraindications for tumor biopsy continue to be under debate. The purpose of this review paper is to critically evaluate the role of uveal melanoma biopsy in ophthalmic oncology.

Sub-threshold micropulse laser treatment reduces inflammatory biomarkers in aqueous humour of diabetic patients with macular edema.

Subthreshold micropulse laser (SMPL) is a tissue-sparing technique whose efficacy is demonstrated for diabetic macular edema (DME) treatment. However, its mechanism of action is poorly known. A prospective observational study was performed on naïve DME patients treated with SMPL, to evaluate the changes of aqueous humor (AH) inflammatory and vaso-active biomarkers after treatments. AH samples of eighteen DME eyes were collected before and after SMPL. Ten non-diabetic AH samples served as controls. Full ophthalmic evaluation, spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography were performed in DME group. Glass chip protein array was used to quantify 58 inflammatory molecules. Central retinal thickness (CRT) and visual acuity were also monitored. Several molecules showed different concentrations in DME eyes versus controls (p value < 0.05). Fas Ligand (FasL), Macrophage Inflammatory Proteins (MIP)-1α, Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) and Vascular Endothelial Growth Factor (VEGF) were increased in DME at baseline versus controls and decreased after SMPL treatments (p < 0.05). CRT reduction and visual acuity improvement were also found. Inflammatory cytokines, mainly produced by the retinal microglia, were significantly reduced after treatments, suggesting that SMPL may act by de-activating microglial cells, and reducing local inflammatory diabetes-related response.

Aqueous humour concentrations of PEDF and Erythropoietin are not influenced by subthreshold micropulse laser treatment of diabetic macular edema.

Purpose: To determine if aqueous humour (AH) concentrations of Retinal Pigment Epithelium (RPE)'s biomarkers are modified after subthreshold micropulse laser (SMPL) treatment of diabetic macular edema (DME).Methods: Naïve DME and healthy subjects were enrolled. All DME patients received SMPL treatments (577-nm yellow light, 5% duty cycle of 0.2 s, power 250 mW), according to study protocol. AH of DME eyes was sampled at baseline and periodically after first SMPL treatment. Control eyes were sampled before cataract surgery. Pigment Epithelium Derived Factor (PEDF) and Erythropoietin (EPO) were quantified with glass-chip protein array.Results: Eighteen DME patients (central retinal thickness ≤ 400 µm on Spectral Domain Optical Coherence Tomography (SD-OCT)) and ten controls were enrolled. The main exclusion criteria were high refractive error, proliferative diabetic retinopathy, glaucoma and neurodegenerative disorders. PEDF concentration was decreased in DME patients at baseline versus controls (P=0.012), while EPO was increased (P=0.029). Both molecules' concentrations remained stable during follow-up after treatments, compared with DME-baseline.Conclusions: The AH concentrations of RPE biomarkers were significantly different in DME treatment-naïve eyes versus controls. The expression of PEDF and EPO remained unchanged after treatments with SMPL in DME eyes. These data are relevant for future research and applications of SMPL.

Single Retinal Layer Changes After Subthreshold Micropulse Yellow Laser in Diabetic Macular Edema.

A pilot prospective, interventional study has been conducted on 10 patients with diabetic macular edema (DME) treated with subthreshold micropulse laser (SMPL) to evaluate changes of individual retinal layers and to correlate with functional changes. All patients underwent complete ophthalmologic evaluation including spectral-domain optical coherence tomography (OCT) and microperimetry at baseline, 3 months, 6 months, 9 months, and 12 months. Compared with baseline, a significant decrease was found in inner nuclear layer (INL) and outer retinal layer (ORL) thickness in the central 1 mm (P < .05). Increase in best-corrected visual acuity was significantly and inversely correlated to central retinal thickness (CRT) (P = .0027), INL (P = .0167), and outer nuclear layer (ONL) thickness (P = .0107). Increase in retinal sensitivity was significantly and inversely correlated to CRT and ONL thickness (P < .01). Therefore, SMPL showed to improve firstly functional parameters and then morphologic parameters. Functional parameters were inversely correlated to CRT, INL, and ONL thickness. The exact mechanism of reduction of INL thickness induced by SMPL remains to be further evaluated. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e218-e225.].

Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two Different Morphologic and Functional Entities.

PURPOSE: To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND-). DESIGN: Cross-sectional, prospective, comparative case series. METHODS: Seventy-two patients (72 eyes: 22 eyes SND+ and 50 eyes SND-) with treatment-naïve, center-involving DME were evaluated. Data gathering included fundus color photographs, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), and microperimetry. The following parameters were evaluated with SD-OCT: central macular thickness (CMT [including SND]); central retinal thickness (CRT [excluding SND]); choroidal thickness (CT); nasal and temporal retinal thickness (RT) at 500 µm and 1500 µm from the fovea; the number of hyperreflective retinal spots (HRS) in the central 3000 µm; and the presence of SND and integrity of the external limiting membrane (ELM). Retinal sensitivity (RS) was evaluated within 4 degrees and 12 degrees of the fovea. Correlation among CT, RS, and HRS in patients with and without SND was determined. RESULTS: CMT (P = .032), temporal RT at 1500 µm (P = .03), mean CT (P = .009), and mean number of HRS (P = .0001) were all higher in SND+ vs SND- eyes. CRT, BCVA, HbA1c, and prevalence of systemic arterial hypertension were not different between the 2 groups. RS within 4 degrees (P = .002) and 12 degrees (P = .015) was lower in SND+ vs SND- eyes. SND correlated significantly with disruption of the ELM (54.55% vs 24%, P = .01) and lower RS. A direct correlation was found between the number of HRS, presence of SND, CT, and RS within 12 degrees in SND- eyes, and an inverse correlation was found between CT and RS within 12degrees in SND+ eyes. CONCLUSIONS: These data may improve characterization of DME in eyes with SND. DME with SND correlates with greater CT, more HRS, disruption of the ELM, and significant macular functional impairment (RS decrease) vs SND-.

Psychotropic drugs prescription in undocumented migrants and indigent natives in Italy.

To evaluate psychotropic drug use in undocumented migrants and natives in the same conditions of poverty. We studied drug dispensation by a nongovernmental organization during the year 2014. Drugs were identified according to the Anatomical Chemical Therapeutic classification and their quantity was measured in defined daily doses (DDD). We determined the percentage of patients taking at least one medicine with psychotropic activity in relation to the total number of patients receiving medicines of any class. We also calculated the individual DDD for psychoactive drugs. The percentage of natives receiving this type of medicine is significantly higher than that of undocumented migrants. Individual DDDs for each class of psychotropic drug are comparable in Italians and undocumented migrants and, among the latter, no difference was found in relation to ethnicity. Our findings describe for the first time the use of psychotropic medicines by undocumented migrants. On this basis, we hypothesize that poverty is more important than migration and ethnicity in generating the need for this type of pharmacological treatment. Both natives and undocumented migrants show poor adherence to treatment. This situation should be considered when programming health interventions in this field for the very poor and undocumented migrants.

A decade-long telemedicine screening program for diabetic retinopathy in the north-east of Italy.

AIM: To describe a decade long telemedicine screening for diabetic retinopathy (DR) in the metropolitan area of Padova (North-East Italy) and to report about prevalence/incidence of DR and maculopathy, rate of progression to STDR and optimal screening interval in patients with no DR at first examination. METHODS: Observational, longitudinal, cohort study; 9347 patients with Type 1 and Type 2 diabetes mellitus (DM) underwent 17,344 fundus exams (three-45° color photos per eye) in two diabetes clinics and were graded in the Reading Centre, by certified personnel. The incidence of STDR, progression of maculopathy and risk factors were evaluated by log Rank test (Kaplan-Meier method). A receiver operating curve was used to determine the optimal screening interval in patients who at the first examination had no DR. RESULTS: The overall prevalence of DR was 27.6%:12.5% mild non proliferative (NPDR), 11.3% moderate NPDR, 2.9% severe NPDR and 0.9% proliferative (PDR). The overall prevalence of maculopathy was 5.7%: 2.8% mild, 2.2% moderate, and 0.7% severe maculopathy. The 10-year incidence of STDR was: 0.6% in no DR, 5.5% in mild NPDR and 21.1% in moderate NPDR at first examination. The 10-year incidence of maculopathy was: 2.1% mild, 1.7% moderate and 0.2% severe. The incidence of STDR in patients with type 1 and type 2 DM and duration>10years was 8.21% and 8.15%;in type 1 DM with duration <10years was 5.5% and in type 2 DM and duration <10years was 1.91%.In patients with no DR at first screening, the best (sensitivity-specificity) follow-up interval is 2.5years. CONCLUSIONS: Screening every 2.5-year in patients without DR at the first examination seems to be adequate. Duration of disease is a relevant risk factor for progression to STDR, however patients with type 1 DM and duration <10years have greater incidence of STDR than patients with type 2 DM and similar disease duration. Epidemiologic data from this decade-long screening program in the North East of Italy may serve for implementing a national screening program.

Post-prandial anorexigenic gut peptide, appetite and glucometabolic responses at different eating rates in obese patients undergoing laparoscopic sleeve gastrectomy.

Although different hypotheses have been proposed, the underlying mechanism(s) of the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still unknown. The aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analogue scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post, rather than pre-operative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in both pre- and post-operative states, with no differences in hunger. In both pre- and post-operative states, there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss.

Predictive algorithms for early detection of retinopathy of prematurity.

PURPOSE: To evaluate sensitivity, specificity and the safest cut-offs of three predictive algorithms (WINROP, ROPScore and CHOP ROP) for retinopathy of prematurity (ROP). METHODS: A retrospective study was conducted in three centres from 2012 to 2014; 445 preterms with gestational age (GA) ≤ 30 weeks and/or birthweight (BW) ≤ 1500 g, and additional unstable cases, were included. No-ROP, mild and type 1 ROP were categorized. The algorithms were analysed for infants with all parameters (GA, BW, weight gain, oxygen therapy, blood transfusion) needed for calculation (399 babies). RESULTS: Retinopathy of prematurity (ROP) was identified in both eyes in 116 patients (26.1%), and 44 (9.9%) had type 1 ROP. Gestational age and BW were significantly lower in ROP group compared with no-ROP subjects (GA: 26.7 ± 2.2 and 30.2 ± 1.9, respectively, p < 0.0001; BW: 839.8 ± 287.0 and 1288.1 ± 321.5 g, respectively, p = 0.0016). Customized alarms of ROPScore and CHOP ROP correctly identified all infants having any ROP or type 1 ROP. WINROP missed 19 cases of ROP, including three type 1 ROP. ROPScore and CHOP ROP provided the best performances with an area under the receiver operating characteristic curve for the detection of severe ROP of 0.93 (95% CI, 0.90-0.96, and 95% CI, 0.89-0.96, respectively), and WINROP obtained 0.83 (95% CI, 0.77-0.87). Median time from alarm to treatment was 11.1, 5.1 and 9.1 weeks, for WINROP, ROPScore and CHOP ROP, respectively. CONCLUSION: ROPScore and CHOP ROP showed 100% sensitivity to identify sight-threatening ROP. Predictive algorithms are a reliable tool for early identification of infants requiring referral to an ophthalmologist, for reorganizing resources and reducing stressful procedures to preterm babies.

HYPERREFLECTIVE RETINAL SPOTS IN NORMAL AND DIABETIC EYES: B-Scan and En Face Spectral Domain Optical Coherence Tomography Evaluation.

PURPOSE: To evaluate hyperreflective retinal spots (HRS), in normal subjects and diabetic patients without and with macular edema (diabetic macular edema, DME), on linear B-scans and corresponding en face image of spectral-domain optical coherence tomography. METHODS: Retrospective evaluation of images of 54 eyes/subjects (16 normal subjects, 19 diabetic patients without DME, and 19 with DME). On horizontal B-scan spectral-domain optical coherence tomography, passing through the center of the fovea, the following characteristics of HRS were evaluated: location (inner retina or outer retina), size (≤30 or >30 µm), reflectivity (similar to nerve fiber layer or to retinal pigment epithelium-Bruch complex), and presence or absence of back shadowing. On en face spectral-domain optical coherence tomography, the following patterns were evaluated: 1) isolated HRS (not corresponding to any visible lesion); 2) HRS corresponding to a segment of retinal capillary or microaneurysm wall; and 3) HRS corresponding to hard exudate. All gradings were performed twice by two graders in a masked fashion. RESULTS: Size ≤30 µm, reflectivity similar to nerve fiber layer, and absence of back shadowing were associated with absence of vessels or any other lesion on en face image (P = 0.0001 for all). Size >30 µm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina were all associated with presence of hard exudate on en face imaging (P < 0.0001 for all). Multiple logistic regression analysis showed that HRS present in the inner retina (P < 0.0001), size >30 µm (P = 0.0029), and presence of back shadowing (P < 0.0001) are directly associated with presence of microaneurysms on en face image. Intragrader and intergrader repeatability were excellent for all evaluations. CONCLUSION: Hyperreflective retinal spots ≤30 µm, reflectivity similar to nerve fiber layer, and absence of back shadowing may represent activated microglial cells; HRS >30 µm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina may represent hard exudate; HRS >30 µm, presence of back shadowing, and location in the inner retina may represent microaneurysms. These hypotheses may be tested in further studies.

Long-term longitudinal modifications in mesopic microperimetry in early and intermediate age-related macular degeneration.

PURPOSE: To evaluate functional changes (retinal sensitivity and fixation characteristics) determined by microperimetry in patients with early and intermediate AMD over 6 years. METHODS: Prospective, longitudinal follow-up (FU) study of 16 patients (29 eyes) with early and intermediate AMD (AREDS 2 and AREDS 3 classification). All eyes underwent: complete ophthalmic examination with best corrected visual acuity (BCVA) determination, color fundus photo (CFP), optical coherence tomography and microperimetry. All CFP were evaluated by two retinal specialists masked to functional data for changes in severity of clinical features over the course of FU. RESULTS: Of 17 eyes graded as AREDS 2 at baseline, 14 (82.35 %) remained stable, and 3 (18.75 %) progressed to AREDS 3. Of 12 eyes graded as AREDS 3 at baseline, 10 remained stable (83.33 %), and 2 (16.67 %) progressed to AREDS 4. Mean BCVA significantly deteriorated in both AREDS 2 (p = 0.006) and AREDS 3 (p = 0.016), with greater decrease in AREDS 3 (p = 0.01)6. Mean retinal sensitivity (RS) significantly decreased over time in both AREDS 2 (p < 0.0001) and AREDS 3 group (p = 0.002), with greater decrease in AREDS 3 (p = 0.006). The mean number of dense scotomas did not change in AREDS 2 (p = 0.3), but significantly increased in the AREDS 3 group (p = 0.035). Points with decreased RS were located in all but the central point (p < 0.0001 for all), without significant differences in number among rings. In the AREDS 2 group, fixation stability remained unchanged. In the AREDS 3 group, four eyes deteriorated from stable to unstable fixation at FU (p = 0.045). CONCLUSION: A significant deterioration in RS is reported in early and intermediate AMD eyes, whereas fixation stability changed only in intermediate AMD (AREDS 3) over long-term follow-up. Microperimetry examination can become a new functional biomarker in early and intermediate AMD patients.