Serum and Macular Carotenoids in Relation to Retinal Vessel Caliber Fifteen Years Later, in the Second Carotenoids in Age-Related Eye Disease Study.

Purpose: We investigated whether dietary carotenoids lutein and zeaxanthin (L/Z) in the serum and macula were associated with central retinal arteriole and venule calibers in a follow-up ancillary study among older women in the Women's Health Initiative. Methods: Among 390 women who participated in Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) (2016-2019), we investigated associations between serum L/Z at Women's Health Initiative baseline (1994-1998), and macular pigment optical density (MPOD) at CAREDS baseline (2001-2004), with central retinal vessel caliber in CAREDS2. MPOD was measured using heterochromatic flicker photometry (0.5° from the foveal center) in CAREDS baseline and CAREDS2. Vessel calibers were measured from fundus photographs (CAREDS2). We also explored associations in women with stable MPOD (±0.10 optical density units) over 15 years (n = 106), given the long-term increases in MPOD related to diet patterns and supplement use. Associations were investigated using linear modeling. Results: In the full sample (n = 390), higher serum L/Z (tertile 3 vs. 1) was positively associated with arteriole caliber (mean ± SE, 145.0 ± 1.4 µm vs. 140.8 ± 1.4 µm; P = 0.05) and venule caliber (214.6 ± 2.2 µm vs. 207.5 ± 2.2 µm; P = 0.03). MPOD was also associated with wider vessel calibers (tertile 3 vs. 1), but the trend was only statistically significant for venules (144.4 ± 1.4 µm vs. 141.1 ± 1.4 µm [P = 0.12] and 213.3 ± 2.1 µm vs. 206.0 ± 2.1 µm [P = 0.02], respectively.) Most associations were strengthened in women with stable MPOD over 15 years, including between MPOD and arteriole caliber (149.8 ± 2.6 µm vs.135.8 ± 3.0 µm; P = 0.001). Conclusions: Higher L/Z status in serum and retina was associated with larger central retinal vessel calibers. Prospective studies and clinical trials are needed to elucidate whether L/Z supplementation prevents vision loss through increasing blood flow.

Principal Cause of Poor Visual Acuity after Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report Number 23.

PURPOSE: To analyze the principal cause for poor vision in eyes with best-corrected visual acuity (BCVA) of 20/200 or worse 2 years after neovascular age-related macular degeneration (nAMD). DESIGN: Prospective cohort study of participants enrolled in a clinical trial of oral supplements. PARTICIPANTS: Age-Related Eye Disease Study 2 (AREDS2) participants whose eyes began anti-vascular endothelial growth factor (VEGF) therapy for incident nAMD and had data available at 2 years. METHODS: Participants underwent refracted BCVA testing, ophthalmoscopic examination, and fundus photography at baseline and annual visits. Self-reports of anti-VEGF injections were collected. MAIN OUTCOME MEASURES: Principal cause of BCVA of 20/200 or worse at 2 years, detected on fundus photography grading. RESULTS: Of the 594 eligible eyes, the number with BCVA of 20/200 or worse at 2 years was 56 (9.4%). Mean BCVA was 14.9 letters (standard deviation [SD], 12.3 letters; Snellen equivalent, 20/500), versus 70.1 letters (SD, 12.8 letters; Snellen equivalent, 20/40) in the other group. Of the 55 eyes with fundus photography available at 2 years, 33 (60.0%) had central macular atrophy and 22 (40.0%) had central subretinal fibrosis assessed as the principal cause for poor vision. The group with poor BCVA had a higher proportion of non-White participants (8.9% vs. 1.7%; P = 0.006), lower BCVA 2 years earlier (mean, 38.0 letters [SD, 26.7 letters; Snellen equivalent, 20/160] vs. 71.8 letters (SD, 11.9 letters; Snellen equivalent, 20/40]; P < 0.0001), higher proportion with macular atrophy 2 years earlier (26.8% vs. 12.3%; P = 0.003), higher proportion with macular hemorrhage (25.5% vs. 13.2%; P = 0.014), and fewer anti-VEGF injections (7.6 vs. 10.2; P = 0.001). CONCLUSIONS: Visual acuity data and fundus photography were obtained in a clinical trial environment, but were related to anti-VEGF therapy given in routine clinical practice. At 2 years after starting anti-VEGF therapy, almost 1 in 10 eyes showed BCVA at the level of legal blindness. From fundus photography grading, the cause of poor vision appeared to be macular atrophy in 60% and subretinal fibrosis in 40%. These data may be useful in understanding the long-term limits to good vision in nAMD.

Association of 2-Year Progression Along the AREDS AMD Scale and Development of Late Age-Related Macular Degeneration or Loss of Visual Acuity: AREDS Report 41.

Importance: The Age-Related Eye Disease Study age-related macular degeneration (AREDS AMD) scale is designed to classify AMD severity. The present cohort study explored whether 2-year progression along this scale was useful for estimating the risk of future progression to late AMD or best-corrected visual acuity (BCVA) loss. Objective: To assess whether 2-year progression along the AREDS AMD scale can be used to estimate the probability of long-term clinically meaningful outcome measures for clinical trials or epidemiologic studies. Design, Setting, and Participants: Age-Related Eye Disease Study participants enrolled in a clinical trial of oral micronutrient supplements had annual color fundus photographs graded centrally using the AREDS AMD scale. Two-year progression (≥2-step and ≥3-step increases in AMD score between baseline and the 2-year study visit) was evaluated as a method of estimating the risk of long-term progression to late AMD or BCVA loss. The AREDS (1992-2001) was a randomized, placebo-controlled clinical trial based at 11 retinal specialty clinics in the United States. The dates of analysis in the present cohort study were November 1992 through November 2005. Main Outcomes and Measures: Development of neovascular (NV) AMD, central geographic atrophy (CGA), any geographic atrophy (GA), or BCVA loss of at least 2 lines or at least 3 lines. Results: Among 3868 participants in the AREDS free of late AMD at baseline, the mean (SD) age was 68.3 (5.0) years, and 2180 of 3868 (56.4%) were women. In the first 2 years after randomization to the AREDS, 669 of 7458 (9.0%) of eyes had at least 2-step 2-year progression, and 275 of 7458 (3.7%) of eyes had at least 3-step 2-year progression. In the 5-year follow-up period (years 2-7), 486 of 7223 (6.7%) of eyes developed NV AMD, 339 of 7253 (4.7%) developed CGA, 726 of 7246 (10.0%) developed any GA, 2622 of 7095 (37.0%) had at least 2-line BCVA loss, and 1494 of 7155 (20.9%) had at least 3-line BCVA loss. After adjusting for demographic and clinical confounders and stratifying by baseline AMD score, statistically significant associations were observed between at least 2-step and at least 3-step 2-year progression of AMD score and subsequent 5-year development of NV AMD: hazard ratios (HRs) ranged from 3.6 (99% CI, 2.4-5.2) to 19.4 (99% CI, 7.7-48.9). For CGA, HRs ranged from 2.6 (99% CI, 1.7-4.0) to 4.7 (99% CI, 2.5-8.9); the results were similar for any GA. For at least 2-line and at least 3-line BCVA loss, HRs ranged from 1.3 (99% CI, 1.0-1.7) to 2.8 (99% CI, 1.8-4.3). For all outcomes, at least 3-step 2-year progression had stronger associations than at least 2-step 2-year progression. These findings were also validated in the AREDS2 cohort. Conclusions and Relevance: Two-year progression of AMD score was associated with progression to clinically meaningful anatomic (late AMD) and vision (≥2-line or ≥3-line loss) outcomes, suggesting that this scale may be useful for future clinical trials designed to slow the progression of AMD.

Comparing the inverted internal limiting membrane flap with autologous blood technique to internal limiting membrane insertion for the repair of refractory macular hole.

PURPOSE: To compare the anatomical and functional outcomes of the inverted internal limiting membrane (ILM) flap technique and the autologous blood clot (ABC) to ILM insertion technique for the repair of refractory macular hole (RMH). METHODS: Fifty-two consecutive patients (52 eyes) diagnosed with RMH with a minimum diameter more than 700 µm were enrolled. All patients underwent vitrectomy and gas tamponade. Of these, 25 patients undergo inverted ILM flap combination with ABC (Group A). The remaining 27 patients underwent ILM insertion (Group B). The main outcome measures were macular hole (MH) closure, foveal configuration, logarithm of the minimum angle of resolution (logMAR), best-corrected visual acuity (BCVA), superficial foveal avascular zone (FAZ) and superficial parafoveal vessel density. RESULTS: Three months post-operation, MH was successfully anatomic closed in 24 of 25 eyes (96%) in Group A and 25 of 27 eyes (92.5%) in Group B (P = 0.599). A concave foveal configuration of MH closure was observed in 23 of 25 eyes (92%) in Group A and 2 of 27 eyes (7.4%) in Group B (P < 0.001). Mean BCVA (logMAR) had improved from 1.31 ± 0.61 to 0.68 ± 0.40 in Group A (P < 0.001) and from 1.34 ± 0.39 to 1.29 ± 0.62 in Group B (P = 0.584) at 3 months. Average superficial FAZ area and superficial parafoveal vessel density were 0.29 ± 0.08 mm2 and 51.41 ± 2.79% in Group A and 0.73 ± 0.15 mm2 and 43.77 ± 2.71% in Group B, respectively. There was a significant difference in both the average superficial FAZ area and parafoveal vessel density between Groups A and B (P < 0.001 for both). CONCLUSION: Anatomical foveal configuration, mean BCVA (logMAR), mean superficial FAZ and parafoveal vessel density outcomes for the inverted ILM flap combined with ABC approach were better than the outcomes obtained with ILM insertion in the treatment of RMH. This approach may promote better long-term, vision function outcomes for patients diagnosed with RMH.

Prognostic Factors in Patients with Persistent Full-Thickness Idiopathic Macular Holes Treated with Re-Vitrectomy with Autologous Platelet Concentrate.

PURPOSE: To identify the predictors for anatomical and functional outcome after re-vitrectomy with application of autologous platelet concentrate (APC) in eyes with persistent idiopathic macular hole (MH). METHODS: Retrospective study of 103 eyes with persistent MHs after vitrectomy with peeling of internal limiting membrane (ILM) and expansive gas. All patients underwent re-vitrectomy with APC and endotamponade. The anatomical MH closure rate and postoperative best-corrected visual acuity (BCVA) were evaluated. Further, predictive factors influencing the success of the surgery were analyzed. RESULTS: Median BCVA (logMAR) before the surgery was 1.00 (interquartile range [IQR] 0.80-1.30) and the median of minimum diameter between hole edges was 508 µm (IQR 387-631). The final closure rate after re-vitrectomy with APC was 60.2% (62 of 103 eyes). The following predictors were identified to significantly influence the closure rate: tractional hole index (THI), axial length, time between first and second surgery, and the experience of the surgeon (p < 0.05). CONCLUSIONS: Re-vitrectomy with APC led to the closure of 60.2% of the persistent MHs. The closure rate negatively correlates with increasing axial length, time between the first and second surgery, and the decreased THI. Further, experienced surgeons (with a history of >100 pars plana vitrectomies with ILM peeling) had significantly higher closure rates.

Leber's idiopathic stellate neuroretinitis: diagnostic and therapeutic conflicts. / Neurorretinitis estrellada idiopática de Leber: conflictos diagnósticos y terapéuticos.

Three cases of patients with decreased visual acuity and papillitis at onset with subsequent macular star development after a few weeks are presented. Complementary tests were unremarkable in all included patients. Based on this clinical context, they were diagnosed with Leber's idiopathic stellate neuroretinitis, were treated with corticosteroids, as well as with antibiotics in 2cases. All patients showed favourable outcomes, although signs of papillary atrophy were observed in the affected eyes. Leber's idiopathic stellate neuroretinitis diagnosis can be challenging due to the wide spectrum of conditions that have to be ruled out. In addition, macular star may appear later on, which should not exclude its diagnosis. Use of antibiotics and/or corticosteroids is controversial considering its benign nature, but should be considered in selected severe cases. Moreover, the routine use of complementary tests should be carefully evaluated, mainly those that can be aggressive and/or expensive, which should be rationally used.

Structural changes of macula and optic disk of the fellow eye in patients with nonarteritic anterior ischemic optic neuropathy.

PURPOSE: The aim was to assess the ganglion cell complex (GCC) thickness, retinal nerve fiber layer (RNFL) thickness and optic disk features in the affected eyes (AE) and unaffected fellow eyes (FE) of subjects with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) and to compare with healthy control eyes (CE) using spectral domain-optical coherence tomography (SD-OCT). METHODS: This study included 28 patients and age, sex and refraction-matched 28 control subjects. Mean GCC thickness and peripapillary RNFL thickness in four quadrants measured by cirrus SD-OCT were evaluated in both AE and FE of patients and CE. In addition, optic disk measurements obtained with OCT were evaluated. RESULTS: Mean GCC thickness was significantly lower in AE compared with both FE and CE (P < 0.001), and mean GCC thickness in FE was significantly lower than CE (P = 0.022). In addition, mean RNFL thickness in superior and nasal quadrants significantly decreased in FE compared with CE (P = 0.020 and 0.010, respectively). Furthermore, AE had significantly greater optic disk cupping compared with both FE and CE (P < 0.001). CONCLUSIONS: GCC and RNFL thickness decreased significantly at late stages of NAION, in both AE and FE compared with CE, suggesting that some subclinical structural changes may occur in FE despite lack of obvious visual symptoms. In addition, there was no significant difference in optic disk features between the CE and FE. And significantly greater optic disk cupping in the AE compared with both FE and CE supports the acquired enlargement of cupping after the onset of NAION.

Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial.

PURPOSE: To assess the efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS: Randomised, double-blinded, placebo-controlled crossover trial of 100 adults (> 50 years) with mild/moderate AMD and vision > 20/70 Snellen equivalent in at least one eye. Exclusion criteria included confounding visual lesions, or significant gastrointestinal disease impairing absorption. Participants were given oral saffron supplementation (20 mg/day) for 3 months or placebo for 3 months, followed by crossover for 3 months. Participants already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these. Primary outcomes included changes in best-corrected visual acuity (BCVA) and changes in multifocal electroretinogram (mfERG) response density and latency. Secondary outcomes included safety outcomes and changes in mfERG and BCVA amongst participants on AREDS supplements. RESULTS: Mean BCVA improved 0.69 letters (p = 0.001) and mean-pooled mfERG latency reduced 0.17 ms (p = 0.04) on saffron compared to placebo. Amongst participants on AREDS supplements, mean BCVA improved 0.73 letters p = 0.006) and mean-pooled mfERG response density improved 2.8% (p = 0.038). There was no significant difference in adverse event occurrence (p > 0.10). CONCLUSION: Saffron supplementation modestly improved visual function in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.

Effects of Crocin on Diabetic Maculopathy: A Placebo-Controlled Randomized Clinical Trial.

OBJECTIVE: Diabetic macular edema (DME) is one of the most important sight-threatening complications in patients with diabetes. Owing to neuroprotective properties, crocin, as the main constituent in saffron, is thought to be useful in the treatment and prevention of diabetic maculopathy. The aim of this trial was to evaluate the effects of crocin as a supplement on reducing inflammation in patients with diabetic maculopathy. DESIGN: Double-masked, placebo controlled, phase 2 randomized clinical trial. METHODS: Participants: In this study, 101 eyes of 60 patients with refractory diabetic maculopathy to conventional therapy including macular photocoagulation and intravitreal injection of anti-vascular endothelial growth factor agent (bevacizumab) with or without steroid (triamcinolone) were studied in 3 groups. INTERVENTION: Patients in the crocin groups received 5 mg or 15 mg crocin tablets per day for 3 months, whereas patients in the placebo group received 1 placebo tablet per day during the study. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured before, every month during, and 3 months after intervention. Biochemical blood tests were also evaluated before and after trial. MAIN OUTCOME MEASURES: The BCVA and CMT were evaluated as the primary outcomes, whereas HbA1c and fasting blood sugar (FBS) were studied as the secondary outcomes in this trial. RESULTS: One hundred and one eyes were enrolled in this trial and were divided into 3 groups (crocin 5 mg, n = 34; crocin 15 mg, n = 33; and placebo, n = 34). According to our data, administration of crocin 15 mg tablet per day could significantly decrease HbA1c (P value = .024; 95% confidence interval [CI] 0.3-0.96), and CMT (P value = .005; 95% CI, 32.75-126.99) and improve BCVA (logMAR changes; P value = .012; 95% CI, 0.23-0.69) compared to the placebo group. Although administration of crocin 5 mg tablet per day could clinically improve HbA1c, FBS, CMT, and BCVA, the difference was not significant compared to the placebo group. CONCLUSION: This study indicated the effect of crocin as a potent antioxidant and neuroprotective for treatment of refractory DME in the short term; however, the clinical significance is yet to be proved in a study with larger sample size and longer duration of follow-up and also in treatment-naïve patients.

The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin with Self-Reported and Actual Prevalence of AMD in an Irish Population-Based Sample.

PURPOSE: To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with grading-confirmed and self-reported prevalence of age-related macular degeneration (AMD). MATERIAL AND METHODS: Data collected from a nationally representative prospective cohort study of community-dwelling adults aged 50 years and over in the Republic of Ireland. Participants underwent a computer-assisted personal interview and a center-based health assessment. Plasma concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by high performance liquid chromatography, and retinal photographs were graded using a version of the AMD International Classification and Grading System. Consumption of supplements containing L and/or Z and/or MZ was recorded as supplement use. Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware; Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and incorrectly believed that they were afflicted with the condition; Group 4 (n = 4094): AMD-free and correctly self-reported absence of AMD. RESULTS: Of 4,423 participants with plasma concentrations of L and Z and gradable retinal photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD. Controlling for family history and age, the relationship between grading-confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma concentrations of L in Group 2 (mean = 0.2162 ± 0.132 µmol) and Group 4 (mean = 0.2040 ± 0.121 µmol/L) were significantly lower than Group 1 (mean = 0.4691 ± 0.0.372 µmol/L) and Group 3 (mean = 0.3176 ± 0.0.235 µmol/L). Supplement use was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively, but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively. CONCLUSION: A belief that one suffers from AMD, whether justified or not, is associated with supplement use and with higher plasma concentrations of L.

Persistent Full-Thickness Idiopathic Macular Hole: Anatomical and Functional Outcome of Revitrectomy with Autologous Platelet Concentrate or Autologous Whole Blood.

PURPOSE: To evaluate long-term outcome after revitrectomy with autologous platelet concentrate (APC) or whole blood (WB) in persistent idiopathic macular hole (MH) after vitrectomy with internal limiting membrane (ILM) peeling. PROCEDURES: Retrospective study of 75 eyes with persistent MH after vitrectomy with ILM peeling and gas. All patients underwent revitrectomy with gas and APC (n = 61) or WB (n = 14). Main outcome measures were anatomical closure rate and postoperative best-corrected visual acuity (BCVA). RESULTS: Closure rate after revitrectomy was 85.2% (52/61) in the APC group and 7.1% (1/14) in the WB group. Median follow-up was 58 (range 3-147) months. Median BCVA (logMAR) in patients with finally closed MHs was 0.4 ± 0.3. Patients with defects of the ellipsoid zone had significantly worse postoperative BCVA. Morphological MH configuration (atrophic or elevated edges) did not correlate with final closure rate. CONCLUSIONS: Revitrectomy with APC and gas is a very effective treatment in persistent MH after vitrectomy with ILM peeling and gas.

Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment: A Randomized Clinical Trial.

Importance: Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD). Objectives: To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD. Design, Setting, and Participants: This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD. Interventions: Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. Main Outcomes and Measures: The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors. Results: Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98° eccentricity between 6 months and baseline was 0.036 (95% CI, -0.037 to 0.110) (P = .33). Conclusions and Relevance: Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients. Trial Registration: clinicaltrials.gov Identifier: NCT01269697.

Epilutein for Early-Stage Age-Related Macular Degeneration: A Randomized and Prospective Study.

PURPOSE: The hypothesis that oral supplementation of the epilutein/lutein combination could augment the macular pigment optical density (MPOD) in patients with age-related macular degeneration (AMD) was tested. METHODS: In a prospective randomized interventional study, 40 consecutive patients with early-stage AMD were recruited. After a 2-week run-in period, patients were randomly treated with a daily oral administration of 8 mg epilutein and 2 mg lutein (group 1) or 10 mg lutein (group 2) for 2 months. At baseline (BL) and 1-month (M1) and 2-month visits (M2), all patients underwent a complete ophthalmological examination, including measurement of MPOD in a 7° area (Visucam 200; Carl Zeiss Meditec, Milan, Italy). Xanthophylls were quantified in plasma, as well as the HDL, non-HDL, and erythrocyte fractions at each study visit. RESULTS: Twenty-one patients (mean age 69.4 ± 6.7 years, 35 eyes) were included in group 1. Mean MPOD was 0.203 ± 0.02 optical density units (ODU) at BL, and increased to 0.214 ± 0.04 ODU at M1 (p = 0.008) and 0.206 ± 0.03 ODU at M2 (p = 0.04). Sixteen patients (mean age 72.0 ± 6.3 years, 29 eyes) were included in group 2. Mean MPOD was 0.215 ± 0.03 at BL, which reduced to 0.202 ± 0.03 ODU at M1 (p = 0.003) and 0.207 ± 0.02 ODU at M2 (p < 0.001). A rise in the systemic level of total xanthophylls was observed at M1 for both groups. At M2, total xanthophylls were significantly increased only in group 1 and decreased in group 2. CONCLUSION: In patients with early-stage AMD, the administration of lutein in combination with epilutein was associated with an increased MPOD compared to the administration of lutein alone.

Temporal Relation between Macular Ganglion Cell-Inner Plexiform Layer Loss and Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma.

PURPOSE: To investigate the temporal relationship between inferior macular ganglion cell-inner plexiform layer (mGCIPL) loss and corresponding peripapillary retinal nerve fiber layer (pRNFL) defect on the optical coherence tomography (OCT) deviation map in glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 151 patients with early-stage glaucoma (visual field [VF] mean deviation between -1.5 and -5.5 decibels [dB]). METHODS: Spectral-domain OCT mGCIPL and pRNFL deviation maps were obtained for the baseline (from January 2012 to August 2012) and again for the follow-up (from January 2015 to August 2015). An integrated deviation map thereafter was merged by vascular landmark-guided superimposition of mGCIPL and pRNFL deviation maps onto RNFL imagery. On the basis of an earlier schematic model, the inferotemporal peripapillary area was divided into (1) the macular vulnerability zone (MVZ) and (2) the inferoinferior portion. MAIN OUTCOME MEASURES: Temporal sequence of inferior mGCIPL loss and corresponding pRNFL (i.e., pRNFL in MVZ) defect on integrated deviation map. RESULTS: At baseline, 99 (65.6%) of the 151 eyes showed inferior mGCIPL loss. In addition, 112 eyes (74.2%) and 5 eyes (3.3%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. At the 3-year follow-up, 112 (74.2%) of the eyes showed inferior mGCIPL loss, whereas 123 eyes (81.5%) and 25 eyes (16.6%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. Ninety-four eyes initially showed inferior mGCIPL loss without pRNFL defect in the MVZ; among them, 19 (20.2%) subsequently showed defect during the 3-year follow-up interval. Meanwhile, among the 52 eyes without preexisting inferior mGCIPL loss, only 1 (1.9%; P < 0.001) developed a pRNFL defect in the MVZ during the 3-year follow-up interval. CONCLUSIONS: In eyes with early glaucoma, mGCIPL change is frequently detected before corresponding pRNFL change. This could be the result of a superior sensitivity of mGCIPL deviation map that allows detection of an abnormality in the mGCIPL thickness earlier. In this light, OCT pRNFL analysis alone likely would overlook macular damage. Macular OCT imaging should be included in the imaging algorithm for the serial observation of patients with glaucoma.

Macular pigment density variation after supplementation of lutein and zeaxanthin using the Visucam® 200 pigment module: Impact of age-related macular degeneration and lens status.

PURPOSE: To assess the evolution of macular pigment optical density (MPOD) following supplementation with various macular formulations obtained with the Visucam® 200, and to study the factors affecting MPOD measurements. MATERIALS AND METHODS: In this prospective, randomized, double-masked multicenter study, patients were divided into 2 groups: group A (patients without retinal pathology who underwent cataract surgery 1 month previously) and group B (patients with neovascular age-related macular degeneration [AMD] in one eye). In each group, half of the patients were randomly assigned to receive a food supplementation either with or without carotenoids (5mg of Lutein and 1mg of Zeaxanthin). Outcome measures included MPOD responses obtained with the Visucam® 200 for one year. RESULTS: In total, 126 subjects (52 men, 74 women) with a mean age of 75.3±7.61 years were enrolled. Mean MPOD values at the time of inclusion were statistically lower in group A (0.088 density unit [DU]) compared to group B (0.163 DU, P<0.05). No statistically significant increase in MPOD was noted in either group, even after discontinuation of the supplementation. By multiple regression analysis, age, female gender, lens status and the presence of AMD seemed to significantly affect MPOD measurements. CONCLUSION: No significant improvement in MPOD seems to be detected with the Visucam® 200 after carotenoid supplementation. The MPOD measurement seems to be highly affected by cataract extraction and the presence of AMD.

MACULAR PIGMENT DISTRIBUTION RESPONSES TO HIGH-DOSE ZEAXANTHIN SUPPLEMENTATION IN PATIENTS WITH MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To analyze macular pigment (MP) amount and distribution in patients with macular telangiectasia Type 2 receiving oral zeaxanthin supplementation in a randomized, open-label, interventional trial. METHODS: Eight macular telangiectasia Type 2 patients were randomized to 10 mg or 20 mg of zeaxanthin per day. At each visit, best-corrected visual acuity, contrast sensitivity, fundus biomicroscopy, color fundus photography, autofluorescence imaging, optical coherence tomography, and serum carotenoid levels were tested. Patients were assessed at baseline and after 6, 12, 18, and 24 months of zeaxanthin supplementation. Concentration of MP was analyzed and calculated from autofluorescence imaging obtained at 488-nm excitation wavelength. Serum carotenoid levels were obtained using high-performance liquid chromatography. RESULTS: The majority of patients had definite increases in the intensity of hypofluorescent ring of MP, but none of them deposited MP centrally at the fovea. Although some patients noted subjective improvements in vision, no objective improvements could be documented, and there were no changes in foveal optical coherence tomographic features. Yellowish, hypofluorescent crystals appeared in one patient's macular region with no change in visual acuity. These inner retinal crystals disappeared several months after discontinuing her 20-mg zeaxanthin supplement. CONCLUSION: Based on the current study, zeaxanthin supplementation does not result in any visual benefit in patients with macular telangiectasia Type 2 and does not reestablish a normal peaked distribution of MP in the fovea. One patient developed a novel, reversible, crystalline maculopathy in response to zeaxanthin supplementation that was reminiscent of canthaxanthin crystalline maculopathy.

COMBINED INTRAVITREAL RANIBIZUMAB AND ORAL SUPPLEMENTATION WITH DOCOSAHEXAENOIC ACID AND ANTIOXIDANTS FOR DIABETIC MACULAR EDEMA: Two-Year Randomized Single-Blind Controlled Trial Results.

PURPOSE: To assess the 2-year effectiveness of intravitreal ranibizumab combined with a dietary supplement rich in docosahexaenoic acid (DHA) plus antioxidants in 62 patients with diabetic macular edema. METHODS: In a randomized single-blind controlled study, 33 subjects (42 eyes) received intravitreal ranibizumab alone and 29 (34 eyes) combined with DHA (1,050 mg/day). Monthly ranibizumab (0.5 mg) was given for the first 4 months followed by on as-needed treatment. RESULTS: At 24 months, the difference between groups in the decrease of central subfield macular thickness was significant in favor of the DHA supplementation group (95% confidence interval of the difference 7.20-97.656; P = 0.024), although improvement in best-corrected visual acuity measured in the Early Treatment Diabetic Retinopathy Study letters did not reach statistical significance (95% confidence interval 5.4-11.2, P < 0.66). At 24 months, gains of >5 and >10 letters were significantly higher in the DHA supplementation group as compared with controls when the worse and better seeing eyes were considered but other differences at 12 months and 24 months were not found. CONCLUSION: Intravitreal ranibizumab combined with DHA supplementation reduced central subfield macular thickness after 2 years of follow-up as compared with ranibizumab alone in patients with diabetic macular edema. This anatomical improvement was accompanied by a trend for an amelioration of vision.

Pilot evaluation of short-term changes in macular pigment and retinal sensitivity in different phenotypes of early age-related macular degeneration after carotenoid supplementation.

PURPOSE: To investigate the response of carotenoid supplementation in different phenotypes of early age-related macular degeneration (AMD) by measuring macular pigment optical density (MPOD) and retinal sensitivity. METHODS: Consecutive patients with only medium/large drusen and only reticular pseudodrusen (RPD) and age-matched and sex-matched controls were enrolled. At baseline, participants underwent a complete ophthalmological examination including measurement of best-corrected visual acuity (BCVA), MPOD and retinal sensitivity. Patients were put on vitamin supplementation (lutein 10 mg/day, zeaxanthin 2 mg/day) and 3 months later underwent a repeated ophthalmological examination. RESULTS: Twenty patients with medium/large drusen, 19 with RPD and 15 control subjects were included. At baseline, in controls, mean MPOD and BCVA were significantly higher compared with RPD (p=0.001 and p=0.01) but similar to medium/large drusen (p=0.9 and p=0.4). Mean retinal sensitivity was significantly higher in controls compared with RPD and medium/large drusen (for all p<0.0001). After 3 months of carotenoid supplementation the mean MPOD significantly increased in RPD (p=0.002), thus showing no more difference compared with controls (p=0.3); no significant changes were found in mean retinal sensitivity and BCVA (p=0.3 and p=0.7). Medium/large drusen did not show significant changes on MPOD, retinal sensitivity and BCVA (p=0.5, p=0.7 and p=0.7, respectively). CONCLUSIONS: Patients with early AMD, especially RPD phenotype, show lower macular sensitivity and MPOD than controls. After supplementation, MPOD significantly increased in RPD. These results suggest different pathophysiology for RPD as compared with medium/large drusen and may open new ways to identifying further therapeutic targets in this phenotype of early AMD.