Macular Pigment in Eyes With Macular Hole Formation and Its Change After Surgery.

Purpose: To observe the macular pigment (MP) appearances in eyes with macular hole (MH) and clarify the origin of the appearances. The mechanisms underlying the development of MH are discussed based on the observation of MP. Methods: This observational case series included 33 eyes of 31 patients with MH who underwent vitrectomy. The MP optical density was measured using the two-wavelength fundus autofluorescence technique. The exact localization of MP was evaluated by comparing MP distribution images and optical coherent tomography B-scan images. Results: MP was missing at the MH. The area of the MP defect corresponded with the area of the defect of outer plexiform layer. MP was present in the retinal flap in stage 2 MH that included glia (Müller cells) and plexiform layers and in the operculum in stage 3 MH, which mainly comprised Müller cells. Cystic spaces in the outer plexiform layer surrounding stage 3 and 4 MHs showed a honeycomb appearance on MP images. MP reappeared to form an irregularly shaped pigment plane after surgical closure of MH. The MP optical volume did not change before and after surgery. Fellow eyes with a central dip in MP distribution subsequently developed MH. Conclusions: The characteristic appearances of MP at the MH were attributed to MP in the plexiform layers and Müller cell cones. A central dip of MP distribution might be a sign of Müller cell cone damage that proceeds with MH formation. Translational Relevance: Observation of MP was useful for understanding the mechanisms of MH formation.

Spatial distribution of macular pigment estimated by autofluorescence imaging in elderly Japanese individuals.

PURPOSE: To determine the spatial distribution types of macular pigment (MP) in elderly Japanese individuals and to consider their origin. STUDY DESIGN: Observational case series. METHODS: Local MP optical density (MPOD) at some eccentricities and MP volume were measured using the MPOD module of a MultiColor Spectralis in 96 pseudophakic eyes of 96 participants (age range, 52-86 years; mean age, 72.8 ± 8.3 years). The MP distribution types were determined from the MP spatial profiles. The retinal thickness (RT) at the foveal center, at both 0.5° and 0.9° eccentricities, and the foveal width were measured using optical coherence tomography. RESULTS: The mean local MPOD at the foveal center was 0.79. Spatial distribution was classified into four types: central peak (24.0%), ring-like (40.6%), intermediate (22.9%), and central dip (12.5%). The ring-like type was the most frequent in these Japanese participants. The central-peak type showed lower MPOD than did the other types in the area outside 0.9°. The ring-like type occurred frequently in eyes with small RT at 0.5° and wider foveal width. A rough contour of the Müller cell cone was found more frequently in the central-dip type than in the other types. CONCLUSIONS: The present characteristics of the different distribution patterns could be explained by the hypothesis that MP presents mainly in the Müller cell cone within 0.5° and in Müller cells in the outer and inner plexiform layers in the area outside 0.5°. The anatomic characteristics of Müller cells at the fovea and parafovea likely affect the MP distribution.

Efficacy of intensity-modulated radiation therapy for optic nerve sheath meningioma.

PURPOSE: The present study examined the efficacy and complications associated with intensity-modulated radiation therapy (IMRT) for optic nerve sheath meningioma (ONSM) in 15 cases and compared visual function before and after treatment. METHODS: Consecutively diagnosed patients with ONSM treated with IMRT were evaluated from 2012 to 2017. We categorized ONSM with three growth patterns (diffuse, fusiform, or globular). Visual acuity, visual fields, and optic disc findings were assessed before and after IMRT. Ocular and systemic complications were evaluated during and after treatment. RESULTS: The 15 patients selected for analysis ranged in age from 33 to 77 years. Post-treatment observation periods were 8 to 57 months. After IMRT, tumor enlargement was not detected in any eyes, and tumor reduction was seen in 2 eyes. At final post-treatment follow-up, eyes with fusiform and globular growth maintained better visual acuity compared with pre-treatment, whereas 2 of 5 eyes with diffuse growth showed reduced vision. Five eyes with no apparent optic disc abnormality maintained better visual acuity compared with pre-treatment, whereas 8 of 10 eyes with disc edema and atrophy remained stable or showed reduced vision. Improvements were seen in all 5 eyes with optic discs negative for pre-treatment abnormalities. Final post-treatment visual field abnormalities improved in 11 eyes. All adverse events identified during IMRT improved rapidly during the treatment period. CONCLUSION: IMRT for the treatment of ONSM achieved improvement and preserved visual function. In particular, early treatment with IMRT before the appearance of optic disc abnormalities can be more effective for improving visual function.

Skin Carotenoid Index in a large Japanese population sample.

Carotenoids are anti-oxidative agents. Human skin and eyes contain specific carotenoid species known to prevent various pathologies caused by oxidative stress. We quantified skin and eye carotenoid levels and investigated their potential correlation in a population including 985 Japanese patients and staff members of an ophthalmology clinic (577 men, 408 women, mean age of 69.7 ± 13.6 [SD]). Skin carotenoid (SC) and macular pigment (MP) levels were measured with reflection spectroscopy and autofluorescence imaging methods, respectively. The mean SC index was 343.1 ± 142.1 (SD). SC indices for women were higher than for men (382 vs 315, p < 0.001). Smokers and overweight subjects (BMI ≥ 25) had lower SC indices. Subjects taking lutein supplements had higher SC indices than non-supplementing subjects (415 vs 325, p < 0.001). SC and MP indices were significantly correlated. The obtained data set can be used for reference purposes by Japanese subjects and researchers interested in tissue responses to diets high in carotenoids and lutein supplementation.

Optic coherence tomography appearances of retinal astrocytic hamartoma and systemic features in tuberous sclerosis of Japanese patients.

PURPOSE: To describe the optical coherence tomography findings of retinal astrocytic hamartoma of tuberous sclerosis and to confirm the association between the type of retinal astrocytic hamartoma and systemic manifestations in Japanese patients. STUDY DESIGN: A retrospective observational case series. METHODS: The medical records of 35 patients with tuberous sclerosis who underwent ophthalmological examination were reviewed. The retinal astrocytic hamartomas were classified into four types based on the optical coherence tomography findings, and their association with systemic disease was evaluated. RESULTS: A total of 40 retinal astrocytic hamartomas in 13 eyes of eight patients aged 4-28 years were identified. Optical coherence tomography images were obtained for 23 lesions in 10 eyes of seven patients. Retinal astrocytic hamartomas were seen as protruding lesions of varying heights (maximum thickness, range between 221 to 1043 µm). Of the 23, 15 lesions showed homogeneous reflectivity; in six lesions, hyper-reflective spots that presumably represented intratumoral calcification were noted. Vitreous changes were noted in 13 lesions; vitreous seeding by retinal astrocytic hamartoma was observed in seven eyes. There were no significant differences in the rates of each systemic feature among the optical coherence tomography types. CONCLUSION: Retinal astrocytic hamartomas were classified into four types according to the previous reports; however, this classification may be worthless because the extent of protrusion did not correspond to the intratumoral characteristics, and the involved depth of the retina was not same even in the same type. An association between the type of retinal astrocytic hamartoma and systemic manifestations was not confirmed in this small case series. We considered that the classification of retinal astrocytic hamartoma and its association with systemic manifestations need further study.

Grade of Cataract and Its Influence on Measurement of Macular Pigment Optical Density Using Autofluorescence Imaging.

Purpose: To evaluate the influence of cataracts on measuring macular pigment optical density (MPOD) using a dual-wavelength confocal scanning autofluorescence imaging technique and to establish methods to compensate for the influence of cataracts. Methods: This prospective case series comprised 100 eyes that underwent cataract surgery. Cataracts were graded based on the World Health Organization classification. MPOD levels were measured with the MPOD module of the Spectralis MultiColor instrument (Spectralis-MP), pre- and postoperatively. We investigated the relationship between change in MPOD values and age, cataract grade, and quality of autofluorescence images. Local MPOD levels were evaluated for four strategically chosen eccentricities within the macular region, and the total MPOD volume was evaluated within 8.98° eccentricity from the center. Results: MPOD levels could be obtained in 67 eyes before surgery. Local and volume MPOD levels were higher postoperatively relative to preoperatively in all eyes. The mean ratio of local MPOD levels after and before surgery (correction factor, CF) ranged from 1.42 to 1.77, with larger CFs required for eccentricities closer to the foveal center. The CF for the MPOD volume was 1.31. Age, grade of nuclear cataract (NUC), posterior subcapsular opacity, and image quality index (IQI) significantly contributed to CFs. For example, regression equation for CF at 0.23° = 0.17 + 0.16 × IQI + 0.29 × NUC grade + 0.01 × age (P < 0.001). Conclusions: Cataracts affected MPOD measurements with the Spectralis-MP, but corrected MPOD results could be obtained via regression equations.

Optical Detection of Macular Pigment Formation in Premature Infants.

PURPOSE: To demonstrate the presence of macular pigment in the retina of premature infants, and to examine its changes with age. METHODS: The participants included 40 premature infants. Infants who had received laser photocoagulation for retinopathy of prematurity were excluded. Macular pigment optical density (MPOD) was measured by fundus reflectometry using RetCam3, a digital fundus camera. The reflection imaging was performed for ROP screening. The imaging time points were from a post menstrual age (PMA) of 29 weeks 0 days to 46 weeks 5 days. RESULTS: The MPOD levels could be obtained from 39 premature infants. The levels at the first measurement ranged from 0 to 0.18 (mean 0.076, SD 0.044). The earliest time, when a nonvanishing MPOD level was obtained, was at a PMA of 33 weeks and 2 days, and that level was 0.05. The initial examination MPOD levels showed a moderate correlation with age (R2 = 0.32, P < 0.00017). The mean MPOD levels measured each week during the follow-up period showed a very strong correlation with age (R2 = 0.91, P < 0.0001). A regression line of MPOD = 0.0069 × age - 0.1783 was derived, where age is counted in PMA days. CONCLUSIONS: The MPOD levels of premature infants were for the first time measured in living eyes. Macular pigment increased linearly with age. TRANSLATIONAL RELEVANCE: Macular pigment increased with the development of macular morphology. This result suggested the importance of nutritional management of infants and mothers during perinatal period.

Reliability of a commercially available heterochromatic flicker photometer, the MPS2, for measuring the macular pigment optical density of a Japanese population.

PURPOSE: The macular pigment optical density (MPOD) of a Japanese population was measured using a commercially based heterochromatic flicker photometer, the Macular Pigment Screener (MPS2). The objective of the study was to evaluate the accuracy and test-retest reliability of the MPS2 in Asian pigmented eyes. STUDY DESIGN: Experimental study to validate the medical instrument in humans. METHODS: Twenty-four healthy Japanese participants with no systemic or eye diseases (men: 13, women: 11; mean [SD] age 38.6 [10.9 years]) were included. The concordance of the MPOD, obtained using the MPS2 and Macular Metrics II (MM2), and the test-retest reliability were examined. RESULTS: Determination of the MPOD was unsuccessful in 1 participant; thus, the MPOD of 23 participants was analyzed. The mean (SD) MPOD measured with the detail-mode of the MPS2 was 0.63 (0.18) and with that of the MM2, it was 0.72 (0.23). The former was significantly lower than the latter (P = .003, paired t test). The MPOD measured with the MPS2 and the MM2 showed good concordance (r = 0.79, P < .001, Pearson product moment correlation). Bland-Altman analyses showed no systematic errors between the MPS2 and the MM2. The intraclass correlation coefficient over 5 measurement times with the detail-mode of the MPS2 was 0.80, and the mean coefficient of variation was 9.4%. CONCLUSION: The high concordance with the MM2 and good test-retest reliability found by this study suggest that the MPS2 is acceptable for use in a Japanese population. However, the mean MPOD yielded by the MPS2 was significantly lower than that yielded by the MM2. Therefore, the MPS2 and MM2 are not interchangeable in a single study.

Reliability of a two-wavelength autofluorescence technique by Heidelberg Spectralis to measure macular pigment optical density in Asian subjects.

This study evaluates the accuracy of an objective two-wavelength fundus autofluorescence technique for the purpose of measuring the macular pigment optical density (MPOD) in Asian pigmented eyes. Potential differences between MPOD values obtained via autofluorescence technique and subjective heterochromatic photometry (HFP) were examined. Inter-examiner reproducibility between three examiners and test-retest reliability over five time points were also explored. Subjects were 27 healthy Japanese volunteers aged 24 to 58 (mean ±â€¯standard deviation, 40.2 ±â€¯9.0) years. An MPOD module of the Spectralis MultiColor instrument configuration (Spectralis-MP) was used for the autofluorescence technique, and a Macular Metrics Densitometer (MM) was used for HFP. The mean MPOD values at 0.25° and 0.5° eccentricities using the Spectralis-MP were 0.51 ±â€¯0.12 and 0.48 ±â€¯0.13, respectively. In comparison, the MM based values were 0.72 ±â€¯0.23 and 0.61 ±â€¯0.25, respectively. High correlations between the Spectralis-MP and MM instrument were found (Pearson's correlation coefficients of 0.73 and 0.87 at 0.25° and 0.5° eccentricities, respectively), but there was a systematic bias: the MPOD values by MM method were significantly higher than those by Spectralis-MP at 0.25° eccentricity. High inter-examiner reproducibility and test-retest reliability were found for MM measurements at 0.5° eccentricity, but not at 0.25°. The Spectralis-MP showed less inter-examiner and test-retest variability than the MM instrument at 0.25° and 0.5° eccentricities. We conclude that the Spectralis-MP, given its high agreement with the HFP method and due to its higher reproducibility and reliability, is well suited for clinical measurements of MPOD levels in Asian pigmented eyes.

Evidence of Carotenoid in Surgically Removed Lamellar Hole-Associated Epiretinal Proliferation.

Purpose: To determine the constituents and origin of the yellow pigment in surgically removed lamellar hole-associated epiretinal proliferation (LHEP) in patients with lamellar macular hole (LMH). Methods: This prospective case series comprised nine eyes with LMH in patients aged 41 to 83 years. The presence of LHEP was confirmed by preoperative optical coherence tomography; the distribution of macular pigment was observed by two-wavelength fundus autofluorescence technique before and after surgery. The subjects underwent a 25-gauge vitrectomy, and the surgically removed epiretinal membranous tissue was fixed with formalin. The specimens were examined using resonance Raman microscopy, and paraffin sections were stained with antiglial fibrillary acidic protein. Results: Seven cases presented with LHEP, and the presence of yellow pigment was confirmed using an operating microscope. Carotenoid-specific Raman signals with three major Raman peaks could be identified in the specimens with LHEP. These specimens were positive for glial fibrillary acidic protein staining. Using the fundus autofluorescence technique, a central defect in the distribution of the macular pigment was noted in the exact area of the lamellar hole. This type of defect was no longer visible after surgical repair of the lamellar hole. Conclusions: The constituents of the yellow pigment in the removed LHEP were carotenoids that typically originate from the macular xanthophyll pigments at the fovea. Since LHEP is reported to be composed of Müller cells, we hypothesize that xanthophyll carotenoids at the fovea are contained in the Müller cells.

Heterozygous deletion of the OPA1 gene in patients with dominant optic atrophy.

PURPOSE: Several OPA1 variants cause dominant optic atrophy (DOA), the most common hereditary optic atrophy. Here, we describe a newly discovered OPA1 deletion in 3 patients with DOA. METHODS: A female proband, her brother, and her mother underwent complete ophthalmologic examinations that included optical coherence tomography and visual field assessments using a Humphrey Field Analyzer with both standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP). Genomic DNA from each patient was examined to detect genomic rearrangements involving OPA1; the genetic analysis involved both multiplex ligation probe amplification and conventional Sanger sequencing. RESULTS: Each patient had temporal optic disc pallor and significant thinning of the retinal nerve fiber layer in both eyes, although there was phenotypic variability among the patients that ranged from asymptomatic to moderately decreased visual acuity. For the affected brother and mother, the mean deviation values from SAP were within the normal range, whereas those from SWAP were significantly below the normal range (P < .05). The genetic analysis identified a newly discovered heterozygous deletion that encompasses exons 9-14 and revealed a breakpoint junction that directly connects intron 8 to intron 14. CONCLUSIONS: This newly described deletion is likely to lead to loss of function in the functionally important GTPase domain encoded by exons 9-16, and the heterozygosity suggested that haploinsufficiency caused the phenotypes. The deletion may be associated with mild DOA phenotypes ranging from asymptomatic to moderately decreased visual acuity.