Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

PURPOSE: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. DESIGN: Cross-sectional analysis. PARTICIPANTS: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). METHODS: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. MAIN OUTCOME MEASURE: Proportion of patients with POAG after stratification according to the GRS. RESULTS: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10-4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10-6). CONCLUSIONS: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Five major sequence variants and copy number variants in the EYS gene account for one-third of Japanese patients with autosomal recessive and simplex retinitis pigmentosa.

Purpose: To elucidate the variant spectrum of the EYS gene in a large cohort of Japanese patients with autosomal recessive and simplex retinitis pigmentosa (arRP and sRP). Methods: We performed a direct sequencing analysis of 44 exons of the EYS gene in 469 patients with RP (including 144 arRP, 288 sRP, and 17 autosomal dominant RP (adRP) cases) in eastern and western regions of Japan and a multiplex ligation-dependent probe amplification (MLPA) of patients who had a single heterozygous pathogenic variant. Results: We identified six pathogenic and 16 likely pathogenic variants from a total of 186 nucleotide sequence variants, of which five variants, c.2528G>A (p.(Gly843Glu)), c.4957dupA (p.(Ser1653Lysfs*2)), c.6557G>A (p.(Gly2186Glu)), c.6563T>C (p.(Ile2188Thr)), and c.8868C>A (p.(Tyr2956*)), were prevalent in patients with arRP and sRP. The homozygous and heterozygous combinations of these five variants accounted for 32.4% (140/432) of Japanese patients with arRP and sRP. Five patients with adRP also had these variants. These five variants segregated with the phenotype in 15 families with RP. MLPA revealed seven copy number variations (CNVs) of the EYS exon(s). Conclusions: This study showed that five major sequence variants and CNVs in the EYS gene account for one-third of Japanese patients with arRP and sRP, and these variants are also responsible for RP showing an autosomal dominant inheritance pattern. This is the first report showing the pathogenicity of three missense variants (p.(Gly843Glu), p.(Gly2186Glu), and p.(Ile2188Thr)) and the presence of CNVs in the EYS gene of Japanese patients with arRP and sRP.

CHOROIDAL AND RETINAL ATROPHY OF BIETTI CRYSTALLINE DYSTROPHY PATIENTS WITH CYP4V2 MUTATIONS COMPARED TO RETINITIS PIGMENTOSA PATIENTS WITH EYS MUTATIONS.

PURPOSE: To compare atrophy of the choroid and retina between Bietti crystalline dystrophy (BCD) patients and EYS-related retinitis pigmentosa (RP) patients with a similar degree of central visual field defects, age, and axial length (AL). METHODS: Nine eyes of nine BCD patients with CYP4V2 mutations (BCD group) were examined. Moreover, we selected 10 eyes of 10 RP patients with EYS mutations matched for age, axial length, and mean deviation (measured with the 10-2 SITA standard program; EYS-RP group), and 10 eyes of 10 normal volunteers matched for age and axial length (control group). Macular thicknesses of the choroid and retina were measured via swept-source optical coherence tomography. RESULTS: The macular choroid was significantly thinner in the BCD group than in the EYS-RP and control groups, although the thickness did not significantly differ between the EYS-RP and control groups. The macular retina was significantly thinner in the BCD and EYS-RP groups than in the control group, although the thickness did not significantly differ between the BCD and EYS-RP groups at most sites. CONCLUSION: Bietti crystalline dystrophy patients with CYP4V2 mutations showed more severe macular choroid atrophy as compared to EYS-related RP patients. These different damage patterns suggest differences in choroidal expression between CYP4V2 and EYS.

Next-generation sequencing-based comprehensive molecular analysis of 43 Japanese patients with cone and cone-rod dystrophies.

PURPOSE: To investigate the efficacy of targeted exome sequencing for mutational screening of Japanese patients with cone dystrophy (CD) or cone-rod dystrophy (CRD). METHODS: DNA samples from 43 Japanese patients with CD or CRD were sequenced using an exome-sequencing panel targeting all 193 known inherited eye disease genes and next-generation sequencing methodologies. Subsequently, candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed using distinct filtering approaches, which included the frequency of the variants in normal populations, in silico prediction tools, and cosegregation. RESULTS: Causative mutations were detected in 12 patients with CD or CRD (27.9%). In total, 14 distinct mutations were identified in the genes ABCA4, CDHR1, CRB1, CRX, GUCY2D, KCNV2, PROM1, PRPH2, and RDH5, including four novel mutations, c.3050+1G>A in ABCA4, c.386A>G in CDHR1, c.652+1_652+4del in CRB1, and c.454G>A in KCNV2. Moreover, a putative pathogenic mutation was identified in RGS9BP, a gene recognized as the source of bradyopsia. CONCLUSIONS: Targeted exome sequencing effectively identified causative mutations in Japanese patients with CD or CRD. The results confirmed the heterogeneity of the genes responsible for CD and CRD in Japanese populations, as well as the efficacy of targeted exome sequencing-based screening of patients with inherited retinal degeneration.

Unilateral negative electroretinogram presenting as photophobia.

PURPOSE: We aimed to describe four cases with an acquired unilateral negative electroretinogram (ERG) and severe unilateral photophobia and assess the underlying pathology. METHODS: We performed a retrospective chart view of the four cases by visiting two independent hospitals. RESULTS: Over the last 10 years, a 65-year-old man, 71-year-old woman, 68-year-old man, and 73-year-old woman presented to the hospitals with unilateral photophobia. Symptom onset was relatively obvious in all the patients. Comprehensive examinations, including visual acuity and visual field assessment, optical coherence tomography, and fluorescein angiography, showed minimal change in the eye with photophobia. However, only in the affected eye, the mixed rod-cone response in full-field ERG showed a markedly electronegative pattern, namely the amplitude of a-wave was preserved and larger than that of b-wave, and the rod and cone responses were very low. In fact, the cone responses were almost absent in all four patients. ERG findings indicate dysfunction of both rod and cone visual pathways, and the preserved a-wave in the mixed rod-cone ERG suggests that the disturbance of the rod visual pathway exists in post-photoreceptors. Moreover, although multifocal ERG showed a very low amplitude in the entire area, the preservation of the responses was detected to some extent only in the center. These symptoms and examination findings remained unchanged for more than 4 years. CONCLUSIONS: Four patients with acquired unilateral negative ERG associated with severe photophobia showed similar clinical findings. To our knowledge, no known disorders can explain these conditions.

ASYMMETRIC CONE DISTRIBUTION AND ITS CLINICAL APPEARANCE IN RETINITIS PIGMENTOSA.

PURPOSE: To report the characteristic changes of fundus autofluorescence in the nasal retina of patients with retinitis pigmentosa. METHODS: We investigated 113 eyes of 113 patients with retinitis pigmentosa. We obtained wide-field fundus autofluorescence images and evaluated the status of the retina nasal to the optic disk. The patients were divided into the following three groups: those without nasal sparing (advanced), those with nasal sparing, and those with larger intact areas in addition to the nasal retina (early). Visual acuity, visual field area, age, and the duration of the symptom were compared among the groups. RESULTS: Twenty eyes (17.7%), 51 (45.1%), and 42 (37.1%) were classified as early, nasal sparing, and advanced, respectively. The nasal retina was essentially preserved in the early group. The clinical characteristics' analysis suggested that the disease progression appears from that represented by early groups, then nasal sparing groups, and finally advanced groups. The authors found that the nasal sparing pattern bears a close resemblance to the previously reported cone photoreceptor distribution. CONCLUSION: Wide-field fundus autofluorescence imaging detected nasal sparing in retinitis pigmentosa. The characteristic fundus autofluorescence pattern should reflect cone photoreceptor distribution in the human retina. This finding may be an example of the clinical appearance of asymmetric photoreceptor distribution.

Wide-Field Fundus Autofluorescence for Retinitis Pigmentosa and Cone/Cone-Rod Dystrophy.

Retinitis pigmentosa and cone/cone-rod dystrophy are inherited retinal diseases characterized by the progressive loss of rod and/or cone photoreceptors. To evaluate the status of rod/cone photoreceptors and visual function, visual acuity and visual field tests, electroretinogram, and optical coherence tomography are typically used. In addition to these examinations, fundus autofluorescence (FAF) has recently garnered attention. FAF visualizes the intrinsic fluorescent material in the retina, which is mainly lipofuscin contained within the retinal pigment epithelium. While conventional devices offer limited viewing angles in FAF, the recently developed Optos machine enables recording of wide-field FAF. With wide-field analysis, an association between abnormal FAF areas and visual function was demonstrated in retinitis pigmentosa and cone-rod dystrophy. In addition, the presence of "patchy" hypoautofluorescent areas was found to be correlated with symptom duration. Although physicians should be cautious when interpreting wide-field FAF results because the peripheral parts of the image are magnified significantly, this examination method provides previously unavailable information.

Intra-familial Similarity of Wide-Field Fundus Autofluorescence in Inherited Retinal Dystrophy.

To examine the similarity of wide-field fundus autofluorescence (FAF) imaging in inherited retinal dystrophy between siblings and between parents and their children. The subjects included 17 siblings (12 with retinitis pigmentosa and 5 with cone rod dystrophy) and 10 parent-child pairs (8 with retinitis pigmentosa and 2 with cone rod dystrophy). We quantified the similarity of wide-field FAF using image processing techniques of cropping, binarization, superimposition, and subtraction. The estimated similarity of the siblings was compared with that of the parent-child pairs and that of the age-matched unrelated patients. The similarity between siblings was significantly higher that of parent-child pairs or that of age-matched unrelated patients (P = 0.004 and P = 0.049, respectively). Wide-field FAF images were similar between siblings with inherited retinal dystrophy but different between parent-child pairs. This suggests that aging is a confounding factor in genotype-phenotype correlation studies.

Qualitative and quantitative characteristics of near-infrared autofluorescence in diabetic macular edema.

OBJECTIVE: To study the characteristics of near-infrared autofluorescence (NIR-AF) imaging and its association with spectral-domain optical coherence tomography (SD-OCT) findings and logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) in diabetic macular edema (DME). DESIGN: Retrospective, observational, cross-sectional study. PARTICIPANTS: One hundred twenty-one consecutive eyes of 87 patients with center-involved DME for whom NIR-AF and SD-OCT images of sufficient quality were obtained. METHODS: The NIR-AF images were acquired using Heidelberg Retina Angiograph 2 (Heidelberg Engineering, Heidelberg, Germany), and sectional retinal images were obtained using Spectralis OCT (Heidelberg Engineering). The presence of a mosaic pattern and cystoid signs were determined qualitatively. We quantified the average fluorescence intensity in the central 1-mm subfield. The characteristics of the NIR-AF images were compared with the OCT findings and logMAR VA. MAIN OUTCOME MEASURES: Qualitative and quantitative characteristics of the NIR-AF images and their association with SD-OCT findings and logMAR VA. RESULTS: Fifty-seven eyes with a mosaic pattern in the NIR-AF macular images had worse logMAR VA (0.355±0.239 vs. 0.212±0.235; P = 0.001), a thicker central subfield (CSF) (530±143 µm vs. 438±105 µm; P <0.001), and disrupted external limiting membrane (ELM; P <0.001) compared with 64 eyes without these findings. Forty-one eyes with a cystoid sign in the NIR-AF images had worse logMAR VA (0.393±0.233 vs. 0.221±0.234; P <0.001) and a thicker CSF (557±155 µm vs. 443±100 µm; P <0.001) than those without them; there were no significant differences in the ELM status. The relative fluorescence intensity in the central subfield in the NIR-AF images was correlated negatively with the CSF thickness and logMAR VA (R = 0.492, P <0.001 and R = 0.377, P <0.001, respectively). Eyes with foveal serous retinal detachment had lower levels of relative fluorescence intensity than those without it (0.751±0.191 vs. 0.877±0.154; P = 0.007); there was no association with the presence of foveal cystoid spaces, disrupted ELM, or hyperreflective foci in the outer retinal layers. CONCLUSIONS: Novel qualitative and quantitative NIR-AF characteristics in the macula indicated the clinical relevance and suggested the pathogenesis in DME.

Tomographic comparison of cone-rod and rod-cone retinal dystrophies.

PURPOSE: To investigate the relationship between impairment of cone/rod photoreceptors and changes in optical coherence tomography (OCT) findings. METHODS: We retrospectively reviewed the clinical records of 35 patients with cone-rod dystrophy (CRD) and 35 visual acuity-matched patients with retinitis pigmentosa (RP). The presence or absence of the external limiting membrane (ELM), inner segment ellipsoid (ISe), interdigitation zone (IZ), and foveal cavitation (hyporeflective space in the outer retina) were determined using OCT image evaluation. RESULTS: There were no statistical differences in the number of CRD and RP patients with an intact ELM and ISe. None of the CRD patients had an intact IZ, but 20 % of RP patients did (P = 0.011). In addition, foveal cavitation tended to be observed more frequently in CRD patients than (25.7 %) in RP patients (5.7 %) despite the difference not being significant after the correction of multiple comparison. CONCLUSIONS: Eyes with CRD and RP had significant differences in foveal morphology, even when visual acuity was matched. This result supports the notion that absence of an IZ and the presence of foveal cavitation is related to cone-dominant photoreceptor impairment.

Prevalence and spatial distribution of cystoid spaces in retinitis pigmentosa: investigation with spectral domain optical coherence tomography.

PURPOSE: To investigate the prevalence and spatial distribution of cystoid spaces (CS) in retinitis pigmentosa patients with spectral domain optical coherence tomography. METHODS: A total of 529 eyes of 275 patients with retinitis pigmentosa were examined with spectral domain optical coherence tomography. The presence or absence of CS was judged for each eye. Retinal layer and outer retinal status where the CS existed were also investigated. Statistical analysis was performed using 1 eye per 1 patient. RESULTS: Cystoid spaces were present in 119 of 529 eyes (22.5%) of 74 of 275 patients (26.9%). There were no significant differences between the cases with and without CS except for central foveal thickness (P < 0.001). Cystoid spaces were noted in the inner nuclear layer in almost all eyes (98.6%), and outer nuclear layer/outer plexiform layer was also involved in many eyes (27.8%). Cystoid spaces were sometimes seen in ganglion cell layer (6.9%). Cystoid spaces were predominantly (78.9%) distributed in the relatively preserved retina where external limiting membrane was retained. The presence of epiretinal membrane or posterior vitreous adhesion was associated with the presence of CS (P < 0.001) but showed no relationship with the spatial location of CS (P = 1.000). CONCLUSION: The prevalence of CS in patients with retinitis pigmentosa was 26.9% and contrary to previous reports, most CS were present in inner nuclear layer. In addition, most CS were observed in relatively retained retina, which is compatible to the prevailing notion. Epiretinal membrane or posterior vitreous adhesion was also associated with the development of CS. The distribution of CS in inner and preserved retina may provide insight for the pathogenesis of CS in retinitis pigmentosa.

Wide-field fundus autofluorescence imaging of retinitis pigmentosa.

PURPOSE: To evaluate the clinical usefulness of wide-field fundus autofluorescence (FAF) imaging in patients with retinitis pigmentosa (RP). DESIGN: Cross-sectional case series. PARTICIPANTS: Seventy-five eyes of 75 patients with RP. METHODS: We examined the eyes of the RP patients using the Optos 200Tx imaging system (Optos PLC, Dunfermline, United Kingdom) and identified abnormal FAF patterns such as ring hyperautofluorescence and patchy hypoautofluorescent areas. Patients with hyperautofluorescent rings or foveal hyperautofluorescence were compared with those without such findings. We determined the percentage area occupied by the FAF abnormalities within a defined region of the eye and examined the relationship between the percentage area of these abnormalities and the visual field area. Moreover, we categorized the patients into 3 different groups based on the presence of a patchy hypoautofluorescent lesion larger than 1 disc diameter: Group A consisted of those with patchy lesions smaller than 1 disc diameter, group B consisted of those with patchy lesions larger than 1 disc diameter but present in only 1 quadrant, and group C consisted of those with patchy lesions larger than 1 disc diameter and present in more than 1 quadrant. In addition, various clinical characteristics were compared among these 3 groups. MAIN OUTCOME MEASURES: Predicting the visual field size and duration of the disease in RP patients based on FAF patterns. RESULTS: Patients without hyperautofluorescent rings or foveal hyperautofluorescence had better visual acuity or mean deviation measured with a Humphrey perimeter. The total area of the abnormal FAF image correlated with the visual field area measured with a Goldmann perimeter (R = -0.64, P<0.001). The individuals with the large patchy hypofluorescent areas (i.e., larger than 1 disc diameter) were older than those with small patchy hypofluorescent areas (group A vs. groups B and C, P = 0.002 and P<0.001, respectively) and had experienced the symptoms for longer durations (group A vs. groups B and C, P<0.05 and P<0.001, respectively). CONCLUSIONS: We can estimate the visual field in patients with RP using the objective measurements from wide-field FAF. The presence of patchy hypofluorescent lesions can be used an indicator of the duration of RP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association between perifoveal hyperfluorescence and serous retinal detachment in diabetic macular edema.

OBJECTIVE: To study the association between the fluorescence levels on fluorescein angiography images and the characteristics on spectral-domain optical coherence tomography (SD OCT) images in diabetic macular edema (DME). DESIGN: Retrospective, observational, cross-sectional study. PARTICIPANTS: One hundred sixty-seven consecutive eyes of 116 patients with diabetic retinopathy for whom FA and SD OCT were performed on the same day. METHODS: Fluorescein angiography using the Heidelberg Retina Angiograph 2 and OCT images using Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were obtained. The leakage of fluorescein dye in each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid was quantified and defined as fluorescence levels, which were compared with the retinal thickness and foveal pathomorphologic features evaluated by SD OCT. MAIN OUTCOME MEASURES: The relationship between fluorescence levels and the foveal pathomorphologic features on SD OCT images. RESULTS: One hundred twelve (67%) eyes with center-involved DME had significantly higher fluorescence levels in all subfields of the ETDRS grid than 55 (33%) eyes without DME. Fluorescence levels were correlated modestly with the retinal thickness in individual subfields in eyes with center-involved DME. Thirty-seven eyes with foveal serous retinal detachment (SRD) had greater retinal thickness in all subfields and higher levels of fluorescence in most subfields, except the superior subfield of the inner ring. After adjusting for the central retinal thickness using multivariate analyses, eyes with SRD had significantly (P = 0.0085) higher fluorescence levels in the nasal subfield of the inner ring and the superior, nasal, and inferior subfields of the outer ring (P = 0.0117, P = 0.0020, and P = 0.0017, respectively). However, the fluorescence levels in any subfields of the inner or outer ring did not differ significantly between eyes with and without foveal cystoid spaces. CONCLUSIONS: The correlation between the fluorescence levels and retinal thickness suggests that the vascular hyperpermeability in the perifovea contributes to the pathogenesis of foveal SRD in DME.

Morphologic and functional changes in retinal vessels associated with branch retinal vein occlusion.

OBJECTIVE: To study the morphologic and functional changes in retinal veins of eyes affected with branch retinal vein occlusion (BRVO) by thin sectioning with optical coherence tomography (OCT). DESIGN: Prospective, observational, cross-sectional study. PARTICIPANTS: Twenty-five consecutive patients (25 eyes) with acute BRVO. METHODS: Major retinal veins, arteries, and arteriovenous (A/V) crossing were examined by sequential thin sectioning by Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany). The retinal blood flow was mimicked in vitro and scanned with Spectralis HRA+OCT. MAIN OUTCOME MEASURES: Morphologic characteristics of normal and BRVO-affected retinal vessels seen in OCT sections. RESULTS: Cross-sectional OCT images revealed physiologic retinal vessels as oval configurations with 4 distinctive hyperreflectivities in a line. The vessel walls showed the innermost and outermost hyperreflectivity, and the blood flow showed internal paired hyperreflectivities with an hourglass shape. No eye with disturbed blood flow due to BRVO showed this internal hyperreflectivity pattern. In vitro, OCT sections of the blood within the glass tube without flow showed homogeneous reflectivities. Increased blood flow velocity resulted in the development of heterogeneous internal reflectivity and hourglass-shaped hyperreflectivities. In all eyes with acute BRVO, sequential sectioning with OCT visualized 3-dimensional vascular architecture and the intravascular conditions at the A/V crossing. At the affected A/V crossing, arterial overcrossing was seen in 17 eyes and venous overcrossing was seen in 8 eyes. In eyes with arterial overcrossing, the retinal vein seemed to run deep under the artery at the A/V crossing, and the venous lumen often appeared to be preserved even at the A/V crossing. In all eyes with venous overcrossing, the retinal vein appeared to be compressed and choked between the internal limiting membrane and the arterial wall at the A/V crossing. Optical coherence tomography sectioning showed intravenous thrombi in 21 eyes, and the thrombi were detected downstream of the A/V crossing in all the cases. The detection of thrombus was significantly associated with ischemic pattern in BRVO (P=0.036). CONCLUSIONS: In eyes with BRVO, sequential thin sections with OCT visualized 3-dimensional retinal vasculature. The present OCT findings suggest that BRVO may occur by 2 different mechanisms, depending on the relative anatomic positions of the crossing vessels. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

[Genotype screening of retinal dystrophies in the Japanese population using a microarray].

PURPOSE: To investigate the pathogenic variants of retinal dystrophies in the Japanese population using microarray analysis. SUBJECTS AND METHODS: DNA extracted from the blood samples of 84 families (87 patients) with retinal dystrophies (retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy and Bietti's crystalline retinopathy) was screened by Asper Biotech services. All the variants detected by microarray analysis were verified by direct sequencing. RESULTS: Mutations were detected in 2 of 36 families with autosomal dominant retinitis pigmentosa, 2 of 4 with Leber congenital amaurosis, 11 of 24 with cone-rod dystrophy, 3 of 7 with macular dystrophy and 6 of 7 with Bietti's crystalline retinopathy. CONCLUSION: Genotype screening using microarray analysis can be effectively used to determine the variants of retinal dystrophies, except retinitis pigmentosa, in the Japanese population.

Three Cases of Arteritic Anterior Optic Neuropathy Several Months after COVID-19 Vaccination.

Background: Vaccines have been approved worldwide to control the coronavirus disease-19 (COVID-19). However, the postvaccination side effects remain controversial. Here, we describe three Japanese cases of arteritic anterior ischaemic optic neuropathy (AAION) following COVID-19 vaccination. Case presentation. The first case involved an 87-year-old woman who presented with vision loss in the right eye 2 months after her second COVID-19 vaccine and in the left eye 2 days later. The second case involved an 88-year-old woman who presented with vision loss in both eyes 3 months after receiving a second vaccine. The third case involved an 80-year-old man who presented with vision loss in the right eye 5 months after receiving a second vaccine. The C-reactive protein level and erythrocyte sedimentation rate were elevated in all patients. Biopsy of the temporal artery or auricular cartilage showed arteritic occlusion in case 2 and polychondritis in case 3. These patients were referred to a local Japanese hospital in 2021 over a period of no longer than 3 months. Conclusion: We observed three cases of AAION after the affected individuals received their second COVID-19 vaccine. Further long-term investigations of ophthalmological events after COVID-19 vaccination are warranted.

Retinal sensitivity after resolution of the macular edema associated with retinal vein occlusion.

PURPOSE: To study the correlation of retinal sensitivity with both morphologic changes in the macula and status of retinal capillary perfusion, after resolution of the macular edema associated with retinal vein occlusion (RVO). METHODS: Retinal sensitivity in the macular area was examined with the Micro Perimeter 1 in 24 eyes after resolution of the macular edema associated with RVO. Using spectral-domain optical coherence tomography, 6 mm × 6 mm areas of macula were examined with 256 sequential horizontal scans. Condition of the photoreceptor layer was evaluated depending upon detection of the junctions between inner and outer segments of the photoreceptors (IS/OS). Fluorescein angiography was performed in 19 eyes. RESULTS: Mean retinal sensitivity on the affected side of the retina was significantly decreased (p < 0.001). On the affected side, the mean retinal sensitivity within the area of deteriorated IS/OS was significantly less (3.8 ± 4.8 dB) than that within areas with complete IS/OS (10.1 ± 6.4 dB, p < 0.001). Mean retinal sensitivity within nonperfused areas was extremely low (0.3 ± 1.3 dB), compared with that in perfused retina (10.9 ± 5.9 dB, p < 0.001). In eyes with a broken foveal capillary ring (FCR), the marked decline in retinal sensitivity was seen within the area where the FCR was broken; this was not seen in eyes with an intact FCR. CONCLUSION: Retinal function was decreased markedly in areas with a damaged photoreceptor layer due to RVO, and was lethally decreased within nonperfused areas. Due to the various limitations of the current study, including implementation of fluorescein angiography in limited number of eyes, wide range of follow-up, and heterogeneity of pretreatments, further prospective studies are necessary to confirm the current findings.

Changes in visual acuity and foveal photoreceptor integrity in eyes with chronic cystoid macular edema associated with retinal vein occlusion.

PURPOSE: To investigate the change in integrity and thickness of the foveal outer retina in eyes with chronic cystoid macula edema associated with retinal vein occlusion. METHODS: We reviewed retrospectively the medical records of 30 eyes of 30 patients who had chronic cystoid macula edema associated with retinal vein occlusion and who had a follow-up of more than 12 months without any treatment. Using optical coherence tomography, we assessed the thickness of the outer retina and status of the junction between the inner and outer segments of the photoreceptors and of the external limiting membrane in the fovea. RESULTS: Visual acuity showed a correlation with thickness of the foveal outer retina (R = -0.37) and with the detection of a line of the inner and outer segments of the photoreceptors (R = 0.65) and that of an external limiting membrane (R = 0.75) beneath the fovea. During the observation period (17.2 ± 5.5 months), neither visual acuity nor the condition of the foveal outer retina showed a significant change, and in no eyes were previously detectable lines of the inner and outer segments of the photoreceptors and external limiting membrane just beneath the foveal cystoid space became undetectable. CONCLUSION: Even if a large cystoid space is located in the fovea, its effect on deterioration of the underlying foveal photoreceptor cells is not as strong as is generally thought.

Disrupted foveal photoreceptors after combined cystoid spaces and retinal detachment in branch vein occlusion treated with bevacizumab.

PURPOSE: To investigate how combined cystoid spaces and serous retinal detachment affect photoreceptor status and visual acuity at final visit in macular edema associated with branch retinal vein occlusion. METHODS: Forty-seven consecutive eyes from 47 patients with macular edema associated with branch retinal vein occlusion treated with intravitreal bevacizumab injection were retrospectively reviewed. Foveal pathomorphology on optical coherence tomography images were divided into two groups: those in which combined foveal cystoid spaces and serous retinal detachment were observed at least once (C+S(+)) and those in which they were not observed (C+S(-)). The relationship between foveal pathomorphology and photoreceptor status and logarithm of the minimum angle of resolution at final visit was investigated. RESULTS: Sixteen eyes were categorized as C+S(+), and the final visual acuity of C+S(+) group was significantly worse than that of C+S(-) group compared with no difference at baseline. Intriguingly, combined foveal pathomorphologies during the course were significantly associated with the absence of external limiting membrane and the junction of inner and outer segments at last visit. Using multivariable analysis, final logarithm of the minimum angle of resolution was significantly related to baseline logarithm of the minimum angle of resolution, diabetes, and C+S(+). CONCLUSION: Combined foveal cystoid spaces and retinal detachment during follow-up predict the disrupted foveal photoreceptors and concomitant poor final visual acuity in branch retinal vein occlusion treated with intravitreal bevacizumab injection.