Nicotinamide mononucleotide, a potential future treatment in ocular diseases.

PURPOSE: The burden of ocular diseases has been gradually increasing worldwide. Various factors are suggested for the development and progression of ocular diseases, such as ocular inflammation, oxidative stress, and complex metabolic dysregulation. Thus, managing ocular diseases requires the modulation of pathologic signaling pathways through many mechanisms. Nicotinamide mononucleotide (NMN) is a bioactive molecule naturally found in life forms. NMN is a direct precursor of the important molecule nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme required for enormous cellular functions in most life forms. While the recent experimental evidence of NMN treatment in various metabolic diseases has been well-reviewed, NMN treatment in ocular diseases has not been comprehensively summarized yet. In this regard, we aimed to focus on the therapeutic roles of NMN treatment in various ocular diseases with recent advances. METHODS: How we came to our current opinion with a recent summary was described based on our own recent reports as well as a search of the related literature. RESULTS: We found that NMN treatment might be available for the prevention of and protection from various experimental ocular diseases, as NMN treatment modulated ocular inflammation, oxidative stress, and complex metabolic dysregulation in murine models for eye diseases such as ischemic retinopathy, corneal defect, glaucoma, and age-related macular degeneration. CONCLUSION: Our current review suggests and discusses new modes of actions of NMN for the prevention of and protection from various ocular diseases and can urge future research to obtain more solid evidence on a potential future NMN treatment in ocular diseases at the preclinical stages.

Evaluation of Optic Disc Edema in Long-Duration Spaceflight Crewmembers Using Retinal Photography.

BACKGROUND: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort. The secondary objective is to propose a standardized evaluation process for SANS-induced ODE across International Space Station Partner Agencies. METHODS: Retrospective, double-blinded diagnostic study. Preflight and postflight fundus photographs were presented to subject matter experts who identified and graded ODE. Pairs of images were also compared side-by-side for disc ranking. Grader concordance was assessed for Frisén grading and disc ranking. RESULTS: Expert graders identified Grade 1 ODE in 17.35% of images from 62 crewmembers (9 female, mean [SD] age, 47.81 [5.19] years). Grades 2 and 3 were identified less than 2% of the time. Concordance in Frisén grades among pairs of graders was 70.99%. Graders identified a difference in preflight and postflight fundus photographs 17.21% of the time when using disc ranking. Pairs of graders had complete concordance in disc ranking 79.79% of the time. Perfect intrarater agreement between Frisén grade and disc ranking occurred 77.7% of the time. CONCLUSIONS: These findings demonstrate intergrader and intragrader variability when using the Frisén scale to identify SANS-induced ODE, which is typically milder in presentation than terrestrial cases of idiopathic intracranial hypertension. It is possible to miss early ODE on fundoscopy alone, making it insufficient as a sole criterion for the diagnosis of SANS. A more sensitive and objective method of surveillance is necessary to monitor international crewmembers for ODE, perhaps using a multimodal approach that includes technology such as optical coherence tomography.

Nicotinamide Mononucleotide Protects against Retinal Dysfunction in a Murine Model of Carotid Artery Occlusion.

Cardiovascular abnormality-mediated retinal ischemia causes severe visual impairment. Retinal ischemia is involved in enormous pathological processes including oxidative stress, reactive gliosis, and retinal functional deficits. Thus, maintaining retinal function by modulating those pathological processes may prevent or protect against vision loss. Over the decades, nicotinamide mononucleotide (NMN), a crucial nicotinamide adenine dinucleotide (NAD+) intermediate, has been nominated as a promising therapeutic target in retinal diseases. Nonetheless, a protective effect of NMN has not been examined in cardiovascular diseases-induced retinal ischemia. In our study, we aimed to investigate its promising effect of NMN in the ischemic retina of a murine model of carotid artery occlusion. After surgical unilateral common carotid artery occlusion (UCCAO) in adult male C57BL/6 mice, NMN (500 mg/kg/day) was intraperitoneally injected to mice every day until the end of experiments. Electroretinography and biomolecular assays were utilized to measure ocular functional and further molecular alterations in the retina. We found that UCCAO-induced retinal dysfunction was suppressed, pathological gliosis was reduced, retinal NAD+ levels were preserved, and the expression of an antioxidant molecule (nuclear factor erythroid-2-related factor 2; Nrf2) was upregulated by consecutive administration of NMN. Our present outcomes first suggest a promising NMN therapy for the suppression of cardiovascular diseases-mediated retinal ischemic dysfunction.

Nicotinamide Mononucleotide Prevents Retinal Dysfunction in a Mouse Model of Retinal Ischemia/Reperfusion Injury.

Retinal ischemia/reperfusion (I/R) injury can cause severe vision impairment. Retinal I/R injury is associated with pathological increases in reactive oxygen species and inflammation, resulting in retinal neuronal cell death. To date, effective therapies have not been developed. Nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD+) intermediate, has been shown to exert neuroprotection for retinal diseases. However, it remains unclear whether NMN can prevent retinal I/R injury. Thus, we aimed to determine whether NMN therapy is useful for retinal I/R injury-induced retinal degeneration. One day after NMN intraperitoneal (IP) injection, adult mice were subjected to retinal I/R injury. Then, the mice were injected with NMN once every day for three days. Electroretinography and immunohistochemistry were used to measure retinal functional alterations and retinal inflammation, respectively. The protective effect of NMN administration was further examined using a retinal cell line, 661W, under CoCl2-induced oxidative stress conditions. NMN IP injection significantly suppressed retinal functional damage, as well as inflammation. NMN treatment showed protective effects against oxidative stress-induced cell death. The antioxidant pathway (Nrf2 and Hmox-1) was activated by NMN treatment. In conclusion, NMN could be a promising preventive neuroprotective drug for ischemic retinopathy.

Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity.

KEY POINTS: During long-duration spaceflights, some astronauts develop structural ocular changes including optic disc oedema that resemble signs of intracranial hypertension. In the present study, intracranial pressure was estimated non-invasively (nICP) using a model-based analysis of cerebral blood velocity and arterial blood pressure waveforms in 11 astronauts before and after long-duration spaceflights. Our results show that group-averaged estimates of nICP decreased significantly in nine astronauts without optic disc oedema, suggesting that the cephalad fluid shift during long-duration spaceflight rarely increased postflight intracranial pressure. The results of the two astronauts with optic disc oedema suggest that both increases and decreases in nICP are observed post-flight in astronauts with ocular alterations, arguing against a primary causal relationship between elevated ICP and spaceflight associated optical changes. Cerebral blood velocity increased independently of nICP and spaceflight-associated ocular alterations. This increase may be caused by the reduced haemoglobin concentration after long-duration spaceflight. ABSTRACT: Persistently elevated intracranial pressure (ICP) above upright values is a suspected cause of optic disc oedema in astronauts. However, no systematic studies have evaluated changes in ICP from preflight. Therefore, ICP was estimated non-invasively before and after spaceflight to test whether ICP would increase after long-duration spaceflight. Cerebral blood velocity in the middle cerebral artery (MCAv) was obtained by transcranial Doppler sonography and arterial pressure in the radial artery was obtained by tonometry, in the supine and sitting positions before and after 4-12 months of spaceflight in 11 astronauts (10 males and 1 female, 46 ± 7 years old at launch). Non-invasive ICP (nICP) was computed using a validated model-based estimation method. Mean MCAv increased significantly after spaceflight (ANOVA, P = 0.007). Haemoglobin decreased significantly after spaceflight (14.6 ± 0.8 to 13.3 ± 0.7 g/dL, P < 0.001). A repeated measures correlation analysis indicated a negative correlation between haemoglobin and mean MCAv (r = -0.589, regression coefficient = -4.68). The nICP did not change significantly after spaceflight in the 11 astronauts. However, nICP decreased significantly by 15% in nine astronauts without optic disc oedema (P < 0.005). Only one astronaut increased nICP to relatively high levels after spaceflight. Contrary to our hypothesis, nICP did not increase after long-duration spaceflight in the vast majority (>90%) of astronauts, suggesting that the cephalad fluid shift during spaceflight does not systematically or consistently elevate postflight ICP in astronauts. Independently of nICP and ocular alterations, the present results of mean MCAv suggest that long-duration spaceflight may increase cerebral blood flow, possibly due to reduced haemoglobin concentration.

Rice Bran and Vitamin B6 Suppress Pathological Neovascularization in a Murine Model of Age-Related Macular Degeneration as Novel HIF Inhibitors.

Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular degeneration (AMD) in the elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti-VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti-VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia-inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE-19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed VEGF mRNA induction under a CoCl2-induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization.

FOVEAL AVASCULAR ZONE AREA ANALYSIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY BEFORE AND AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To determine the size of the foveal avascular zone (FAZ) by optical coherence tomography angiography before and after idiopathic epiretinal membrane surgery. METHODS: Thirteen consecutive patients (13 eyes) with unilateral epiretinal membrane were studied retrospectively. Optical coherence tomography angiography was used to measure the FAZ area within 3 mm × 3 mm scans of the superficial (superficial FAZ) and deep plexus layers (deep FAZ) before and 6 months after vitrectomy. The unaffected fellow eyes were used as controls. RESULTS: The mean superficial and deep FAZ areas at 6 months after vitrectomy (0.080 ± 0.038 and 0.113 ± 0.045 mm, respectively) were significantly (P < 0.0001, P = 0.0035) larger than the corresponding mean preoperative FAZ areas (0.056 ± 0.030 and 0.082 ± 0.035 mm). However, the areas of FAZ expansion were small (0.024 ± 0.013 and 0.031 ± 0.031 mm). The mean postoperative superficial and deep FAZ areas were significantly (P < 0.0001, P < 0.0001) smaller than those of fellow eyes (0.295 ± 0.108 and 0.410 ± 0.142 mm). Multiple regression analysis showed that preoperative FAZ area had the highest correlation with postoperative FAZ area (P < 0.05). CONCLUSION: This study showed horizontal contraction of the FAZ area in eyes with epiretinal membrane. Because preoperative FAZ area correlates with postoperative FAZ area, FAZ area may be a useful parameter for determining timing of surgery for epiretinal membrane.

A Multicenter Randomized Controlled Study of Antioxidant Supplementation with Lutein for Chronic Central Serous Chorioretinopathy.

PURPOSE: To investigate functional and morphological changes in patients with chronic central serous chorioretinopathy after supplementation with antioxidants containing lutein or a placebo. PROCEDURES: One hundred eyes of 100 patients were randomly divided into 2 groups, one taking tablets with lutein plus other antioxidants and the other taking a placebo for 6 months. Best-corrected visual acuity (BCVA) and the subfoveal fluid height on optical coherence tomography were measured. RESULTS: Seventy-nine patients (37 in the supplementation and 42 in the placebo group) completed the 6-month follow-up. In the supplementation group, mean BCVA showed significant improvement (p = 0.003), while there was no significant change in the placebo group (p = 0.589). The mean subfoveal fluid height was significantly reduced, by 28.6%, in the supplementation group (p = 0.028), in contrast to 3.3% in the placebo group (p = 0.898). CONCLUSIONS: Antioxidant supplementation significantly reduced subfoveal fluid height. The impacts of antioxidant supplementation on BCVA remain to be elucidated in future studies.

Findings of Optical Coherence Tomographic Angiography at the Choriocapillaris Level in Central Serous Chorioretinopathy.

PURPOSE: To reveal vascular signals at the choriocapillaris level in central serous chorioretinopathy (CSC) using optical coherence tomographic angiography (OCTA). PROCEDURES: We analyzed vascular signals at the choriocapillaris level in 58 CSC and 51 contralateral eyes by OCTA (RTVue XR Avanti with AngioVue; Optovue Inc., Fremont, Calif., USA). Data analysis included age, best corrected visual acuity (BCVA), disease duration and serous retinal detachment (SRD) height. RESULTS: Morphologically, abnormal signals at the choriocapillaris level were detected in all CSC eyes (100%), and then classified into three patterns. Age, BCVA, disease duration and SRD height showed no significant correlation with signal patterns. Thirty-one contralateral eyes (61%) showed abnormal signals at the choriocapillaris level on OCTA, while 20 (39%) had a normal pattern. CONCLUSIONS: OCTA revealed three types of abnormal signals not only in CSC eyes but also in fellow eyes without SRD. OCTA may provide information for elucidating the underlying pathogenesis of CSC.

Characteristics of Hyperautofluorescent Choroidal Vessels Using Fundus Camera Type Short-Wavelength Autofluorescence.

PURPOSE: To clarify differences between eyes showing hyperautofluorescent choroidal vessels in both nasal and temporal, or only the nasal, portions of the fundus using fundus autofluorescence. METHODS: Nineteen eyes with hyperautofluorescent vessels in both nasal and temporal portions (group 1) and 17 only the nasal portion (group 2) of the fundus were studied. Choroidal and retinal thicknesses (foveal, and nasal and temporal 3,000 µm from the fovea), axial length, and refraction were compared between the two groups. RESULTS: In group 1, the average foveal, nasal, and temporal choroidal thicknesses (mean ± SD) were 69.0 ± 30.9, 57.1 ± 18.7, and 88.3 ± 30.4 µm, retinal thicknesses 170.1 ± 48.5, 221.9 ± 46.5, and 209.5 ± 37.9 µm, axial length 28.2 ± 2.2 mm, and refraction -9.9 ± 5.9 dpt. In group 2, the respective values were 174.8 ± 43.0, 80.5 ± 20.9, and 173.5 ± 46.1 µm, 213.4 ± 29.8, 278.3 ± 20.2, and 252.8 ± 19.6 µm, 24.2 ± 1.4 mm, and -1.8 ± 3.8 dpt. There were significant between-group differences for all items (p < 0.05). CONCLUSIONS: Fundus autofluorescence tends to be associated with the detection of hyperautofluorescent choroidal vessels in eyes with strong myopia or greater axial length.

Investigation of the Etiology of Central Serous Chorioretinopathy Using En-Face Optical Coherence Tomography and Indocyanine Green Angiography.

PURPOSE: To identify locations of hypofluorescent lesions on late-phase indocyanine green angiography (ICGA) in patients with central serous chorioretinopathy (CSC) using en-face optical coherence tomography (OCT). PROCEDURES: We retrospectively studied 25 consecutive untreated CSC patients, using swept-source OCT and ICGA. En-face swept-source OCT images were automatically segmented and flattened with Bruch's membrane (BrM). We compared the sizes of hyperreflective areas in the 25 CSC and 25 contralateral eyes on en-face images and hypofluorescent areas on ICGA after 30 min. RESULTS: All 25 CSC eyes and 13 contralateral eyes showed abnormal hypofluorescent areas on late-phase ICGA and hyperreflective areas on en-face OCT from BrM to the choriocapillaris, and these findings correlated with the abnormal areas (r = 0.9988; p < 0.001). CONCLUSIONS: In CSC patients, we detected abnormal hypofluorescence on ICGA in the late phase, which corresponded to abnormal hyperreflective areas from BrM to the choriocapillaris level in en-face images.

Characteristics of Hyperautofluorescent Choroidal Vessels within the Macular Atrophic Area Using Spectral-Domain Optical Coherence Tomography.

PURPOSE: The aim of this study was to clarify the characteristic findings in patients with geographic atrophy with or without hyperautofluorescent choroidal vessels within macular atrophic areas on short-wavelength fundus autofluorescence imaging. PROCEDURES: Sixty-seven eyes of 43 consecutive patients with macular atrophic areas were divided into groups with (group 1) and without (group 2) hyperautofluorescent choroidal vessels on fundus autofluorescence imaging and then retrospectively studied using spectral-domain optical coherence tomography. RESULTS: In group 1 (n = 21), the average subfoveal choroidal thickness was 61.5 ± 20.1 µm, and the average foveal retinal thickness was 93.0 ± 51.3 µm. On the other hand, in group 2 (n = 46), the average subfoveal choroidal thickness was 200.7 ± 83.1 µm, and the average foveal retinal thickness was 109.2 ± 58.5 µm. Although retinal thickness did not differ significantly between the two groups (p = 0.28), the difference in choroidal thickness was statistically significant (p < 0.001). CONCLUSIONS: Choroidal thinning might contribute to the hyperautofluorescence of choroidal vessels.

Morphologic features of focal choroidal excavation on spectral domain optical coherence tomography with simultaneous angiography.

PURPOSE: To reveal clinically relevant morphologic findings in patients with focal choroidal excavation (FCE) using enhanced depth imaging optical coherence tomography. METHODS: Thirty-one FCE lesions in 29 eyes of 26 patients (21 men, 23 eyes; 5 women, 6 eyes) were studies. In all 26 patients, color fundus photographs were obtained, and fluorescein angiography and indocyanine green angiography with simultaneous enhanced depth imaging optical coherence tomography were performed. Twenty-five eyes also underwent angiographic video recording. RESULTS: Focal choroidal excavation was detected in eyes with typical age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, and idiopathic choroidal neovascularization, whereas in 8 eyes, FCE was considered to be idiopathic. Morphologically, FCE lesions were classified into 3 types: cone-shaped, bowl-shaped, and mixed. The cone-shaped type was detected in 17 lesions, bowl-shaped in 8, and mixed in 6, on optical coherence tomography findings. All bowl-shaped and mixed types had retinal pigment epithelial irregularities within the FCE lesion. The cone-shaped type was not observed in eyes with typical age-related macular degeneration. CONCLUSIONS: Morphologically, FCE lesions were classified into cone-shaped, bowl-shaped, and mixed types, based on optical coherence tomography findings. Focal choroidal excavation formation may be associated in part with chorioretinal diseases such as age-related macular degeneration and central serous chorioretinopathy, whereas some eyes are considered to have idiopathic FCE.

Choroidal thickness measurement by enhanced depth imaging and swept-source optical coherence tomography in central serous chorioretinopathy.

BACKGROUND: We evaluated subfoveal choroidal thickness measured with two different forms of optical coherence tomography (OCT), enhanced-depth imaging (EDI) and swept-source (SS) OCT, in central serous chorioretinopathy (CSC). METHODS: Fifty-six eyes of 48 patients diagnosed with acute or chronic CSC, were studied prospectively. Subfoveal choroidal thickness was measured as the distance between the outer border of the retinal pigment epithelium-Bruch's membrane complex, and the chorioscleral border under the fovea. Subfoveal choroidal thickness was measured using EDI-OCT and SS-OCT. We also measured serous retinal detachment (SRD) only with SS-OCT. The Pearson correlation coefficient was used to assess the correlation between subfoveal choroidal thickness values determined by the two different OCT modalities. RESULTS: The mean patient age was 52 ± 13 years (range, 32-82 years). Among the 56 eyes, 21 had acute CSC and 35 had chronic CSC. Subfoveal choroidal thickness measured with EDI-OCT was 336.6 ± 91.6 µm in acute and 388.0 ± 103.4 µm in chronic CSC. With SS-OCT, the thickness in acute CSC was 332.0 ± 96.7 µm and that in chronic CSC was 392.6 ± 101.3 µm. Acute CSC (p <0.001, correlation coefficient; r = 0.99) and chronic CSC (p <0.001, correlation coefficient; r = 0.97) values obtained with the two different OCT modalities correlated significantly. Among the 56 eyes, 43 (19 eyes with acute and 24 with chronic CSC) were evaluable for SRD height by SS-OCT. The mean SRD height was 128.9 ± 83.6 µm in acute cases and 96.3 ± 62.0 µm in chronic cases. CONCLUSIONS: Subfoveal choroidal thickness obtained with two different OCT modalities correlated significantly.

Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response.

Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen.

Subfoveal choroidal thickness and foveal retinal thickness during head-down tilt.

INTRODUCTION: To reveal subtle morphological changes in the eye during simulated microgravity for spaceflights, we measured subfoveal choroidal thickness and foveal retinal thickness during 10 degrees head-down tilt (HDT). We hypothesized that elevated ophthalmic vein pressure during simulated microgravity increases subfoveal choroidal thickness via enlargement of the choroidal vasculature and greater choroidal blood volume. METHODS: The right eyes of nine healthy subjects (seven men, two women) were examined. Subfoveal choroidal thickness and foveal retinal thickness were measured using spectral domain-optical coherence tomography in the sitting position, and after 15 and 30 min of 10 degrees HDT. Intraocular pressure was also measured. RESULTS: Mean subfoveal choroidal thickness (+/- SEM) increased from 300 +/- 31 microm in the sitting position to 315 +/- 31 microm with 15-min HDT, and 333 +/- 31 microm with 30-min HDT. However, no change in foveal retinal thickness was observed (228 +/- 9 microm in the sitting position, 228 +/- 10 microm with 15-min HDT and 228 +/- 9 microm with 30-min HDT). Intraocular pressure increased from 14 +/- 1 mmHg in the sitting position to 21 +/- 2 mmHg with 30-min HDT (54 +/- 6%, N = 5). DISCUSSION: Subfoveal choroidal thickness and intraocular pressure were increased by HDT during simulated microgravity, although no change in foveal retinal thickness was observed.

Multiple Factors Causing Myopia and the Possible Treatments: A Mini Review.

The myopia epidemic has become a global public health problem. Although myopia is progressing worldwide, the recent coronavirus infections 2019 (COVID-19) outbreak has spurred myopia progression. The current evidence-based treatments for humans are atropine eye drops, optical treatment with defocus, use of orthokeratology, extending proximity working distance, pausing from near work every half hour and increased time outside the home. Studies on myopia using animal models have been conducted for more than 40 years. In recent years, new mechanisms of myopia suppression have been revealed from animal experiments such as inflammation control, intraocular pressure control, light control, and the activity of early growth response protein 1 control. This mini-review provides a summary of the scientific evidence currently available on the control of myopia, and the possible treatments mitigating myopia.

Progression of age-related macular degeneration in eyes with abnormal fundus autofluorescence in a Japanese population: JFAM study report 3.

PURPOSE: To evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD. METHODS: Sixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters. RESULTS: Of the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p<0.05). Multivariable analysis revealed that patients who showed non-compliance with the supplement intake were more likely to develop nAMD (p<0.05). No significant association was found between the patchy pattern and CNV development (p = 0.86). CONCLUSION: The fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

Detection of morphologic alterations by spectral-domain optical coherence tomography before and after half-dose verteporfin photodynamic therapy in chronic central serous chorioretinopathy.

PURPOSE: To study the morphologic features of serous retinal detachment, the photoreceptor inner and outer segment junction line, retinal pigment epithelium irregularities, pigment epithelial detachment, and the subfoveal choroid before and after treatment of chronic central serous chorioretinopathy, using spectral-domain optical coherence tomography. METHODS: We studied 17 eyes of 17 consecutive patients (all men) with chronic central serous chorioretinopathy. We performed photodynamic therapy (PDT) with half-dose (3 mg/m2) verteporfin. We studied morphologic features using spectral-domain optical coherence tomography before and at 1, 3, 6, and 12 months after PDT. RESULTS: Retinal detachment showed reattachment in 16 of the 17 eyes by 3 months after PDT. The inner and outer segment junction line could be visualized in 13 eyes at 6 months after PDT. Retinal pigment epithelium irregularities were confirmed in all 17 eyes before and during the year after PDT. Pigment epithelial detachment initially disappeared but then recurred in 5 eyes after PDT. Subfoveal highly reflective substances first lessened in intensity but then again became prominent in 2 eyes. CONCLUSION: The authors identified recurrent pigment epithelial detachment and/or retinal detachment during the 1-year period after PDT. Even if retinal detachment initially disappears, retinal pigment epithelium or choroidal morphologic changes can still develop. The effect of half-dose PDT for chronic central serous chorioretinopathy may thus be temporary.