Enhancement of plasmonic coupling on Si metallized with intense femtosecond laser pulses.

Using a pump-probe technique, the reflectivity of a silicon grating surface irradiated with intense femtosecond (fs) laser pulses was measured as a function of the incidence angle and the delay time between pulses. After irradiating the surface with an intense s-polarized, 400 nm, 300 fs laser pulse, the reflectivity measured with a weak p-polarized, 800 nm, 100 fs laser pulse exhibited an abrupt decrease for an incidence angle of ~ 24°. The depth of the dip was greatest for a delay time of 0.6-10 ps, for which the reflectivity around the dip was highest. The surface was also found to be ablated most strongly for the conditions causing the deepest dip for a delay time of 5-10 ps. Surface plasmon polaritons (SPPs) on silicon metallized by the intense pulse are resonantly excited by the subsequent pulse, and the strong coherent coupling between the subsequent pulse and SPPs excited on the molten Si surface produced by high-density free electrons induces strong surface ablation due to the intense plasmonic near-field. The results clearly show that fs pulses can be used to significantly modulate the nature of nonmetallic materials and could possibly serve as a basic tool for the excitation of SPPs on nonmetallic materials using ultrafast laser-matter interactions.

A Modified Intrascleral Intraocular Lens Fixation Technique Using 27-Gauge Blunted Needles with Fewer Intraocular Manipulations.

A new method for intraocular lens (IOL) fixation in the scleral tunnel using two common 27G blunted needles and an ultrathin 30G needle with fewer intraocular manipulations was developed. Half-depth scleral flaps were prepared, and vertically angled sclerotomies were performed under each scleral flap, 2 mm from the limbs with a 20G microblade or a 26G needle. Two bent 27G blunted needles connected the sclerotomy and corneoscleral incisions. One haptic was inserted into this bent 27G blunted needle extraocularly and extruded through the sclerotomy site. Each haptic was inserted into the lumen of the preplaced ultrathin 30G needle and buried into the scleral tunnel. In this retrospective study, we reviewed the outcomes of this new technique in patients with at least 3 months' follow-up data. Iris capture of the IOL was not observed in any case, and IOL repositioning was not performed either. Astigmatism induced by intraocular aberration was almost as same as that with other methods. Our technique can be performed in any operation room without any extra instruments. This trial is registered with UMIN000044350.

Deterioration of phagocytosis in induced pluripotent stem cell-derived retinal pigment epithelial cells established from patients with retinitis pigmentosa carrying Mer tyrosine kinase mutations.

Retinitis pigmentosa (RP) is an incurable retinal degenerative disease with an unknown mechanism of disease progression. Mer tyrosine kinase (MERTK), which encodes a receptor of the Tyro3/Axl/Mer family of tyrosine kinases, is one of the causal genes of RP. MERTK is reportedly expressed in the retinal pigment epithelium (RPE) and is essential for phagocytosis of the photoreceptor outer segment. Here, we established induced pluripotent stem cells (iPSC) from patients with RP having homozygous or compound heterozygous mutations in MERTK, and from healthy subjects; the RP patient- and healthy control-derived iPSCs were differentiated into RPE cells. Although cytoskeleton staining suggested that polarity may have been disturbed mildly, there were no apparent morphological differences between the diseased and normal RPE cells. The internalization of photoreceptor outer segments in diseased iPSC-RPE cells was significantly lower than that in normal iPSC-RPE cells. This in vitro disease model may be useful for elucidating the mechanisms of disease progression and screening treatments for the disease.

Angiographic Risk Features of Branch Retinal Vein Occlusion Onset as Determined by Optical Coherence Tomography Angiography.

Purpose: Examine associations between the vasculature at arteriovenous (AV) crossings and the onset of branch retinal vein occlusion (BRVO). Methods: We included 78 patients with major BRVO, 35 patients with macular BRVO, and 110 controls without BRVO and determined the vessel positions at AV crossings, where the first- or second-order branches of the retinal veins associate, using a viewing angle of 12 × 12 mm2 in optical coherence tomography angiography (OCTA). Results: We reviewed 1349 and 1276 AV crossings in BRVO patients and control subjects, respectively. The proportions of venous overcrossing were 26.5%, 28.6%, and 26.8% at non-causative crossings in BRVO eyes, non-BRVO fellow eyes, and unaffected control eyes, respectively; however, the rate of venous overcrossings at the causative crossings was 45.1%. In OCTA analyses, we divided the branches into macular- or non-macular veins. The rate of venous overcrossing was 52.5% at causative crossings in major BRVO but was 28.6% in macular BRVO. Odds ratios for whether venous overcrossing was a risk factor for BRVO were 3.09 (95% confidence interval [CI], 1.96-4.88) and 0.94 (95% CI, 0.44-2.00) for non-macular veins and macular veins, respectively. The patients with major BRVO caused by venous overcrossing were younger than patients for whom the cause was arterial overcrossing (P < 0.001). The onset of macular BRVO did not differ between crossing patterns at causative crossings (P = 0.60). Conclusions: In eyes with BRVO, venous overcrossing was a common angiographic feature at causative crossings and might be a risk factor for major BRVO onset.

Branch Retinal Vein Occlusion: Treatment Outcomes According to the Retinal Nonperfusion Area, Clinical Subtype, and Crossing Pattern.

This prospective study examined 58 eyes with branch retinal vein occlusion (BRVO) to investigate the effects of the nonperfusion area (NPA), clinical subtype, and crossing pattern on the 2-year outcomes of ranibizumab therapy for the macular edema (ME). All eyes received three initial monthly injections, followed by additional pro re nata (PRN) injections. The final best corrected visual acuity (BCVA) and ranibizumab injection number were not associated with the macular NPA or total NPA at baseline or month 12, and they showed no significant differences between the clinical subtypes. However, the incidence of neovascular changes was higher in the major BRVO group than in the macular BRVO group (P = 0.030). Twelve and 19 of the 34 eyes with major BRVO exhibited arterial overcrossing and venous overcrossing, respectively. At baseline, the total NPA did not differ according to the crossing pattern, however, the total NPA was significantly larger in the venous overcrossing group at month 12 (P = 0.047). At month 24, the incidence of neovascular changes was higher in the venous overcrossing group (P = 0.030). Following ranibizumab therapy for BRVO-associated ME, the clinical subtype and the arteriovenous crossing pattern may be associated with neovascular changes.

FIXATION STATUS AFTER RESOLUTION OF MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To evaluate fixation status of eyes with branch retinal vein occlusion (BRVO) and to investigate its association with other clinical parameters. METHODS: This study included 57 consecutive eyes with BRVO after resolution of macular edema. Fixation status was determined by microperimetry. Defect length of the foveal ellipsoid zone band was measured by optical coherence tomography, and retinal perfusion status was assessed by optical coherence tomography angiography. RESULTS: In microperimetry, the mean fixation rate around the gravitational center of all fixation points (defined as the fixation center) was found to be 79.8 ± 18.9%, which was significantly associated with defect length of the foveal ellipsoid zone band (P < 0.001) and distance between the foveal and fixation centers (P = 0.012). The integrity of the ellipsoid zone band at the fixation center was intact in 55 eyes (96.5%). Fixation centers were located within and outside the foveal avascular zone in 33 (57.9%) and 24 (42.1%) eyes, respectively; among the latter eyes, all fixation centers were perfused. Downward deviation of fixation points was rare, despite variations in the occluded area; there was a significant difference in distribution of deviation between eyes with superotemporal and inferotemporal BRVO (P < 0.001). CONCLUSION: In eyes with BRVO, fixation status was strongly associated with visual acuity, morphologic damage, and retinal perfusion status both in the foveal area and at the fixation center after resolution of macular edema. This information regarding fixation status could facilitate vision management in patients with BRVO.

Segmentation of the Four-Layered Retinal Vasculature Using High-Resolution Optical Coherence Tomography Angiography Reveals the Microcirculation Unit.

Purpose: To differentiate the four layers of the retinal vessel network in the human macula and examine their morphologic features using high-resolution optical coherence tomography angiography (HR-OCTA). Methods: Macular areas measuring 464 × 464 pixels of 10 right eyes of 10 healthy subjects without ocular disease were scanned 10 times using a HR-OCTA device. Averaged OCTA images were created. Based on clear decorrelation signals, four vascular slabs were segmented, comprising one each in the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and top and bottom of the inner nuclear layer (INL). Qualitative features and quantitative measurements in each slab were compared with those in conventionally segmented slabs. Results: HR-OCTA isolated four layers of vascular plexuses in the macula that followed the corresponding anatomic layers. Segmentations for the RNFL revealed that radial peripapillary capillaries (RPCs) extended to the central macular area. The RPCs followed relatively straight and long paths, with few apparent feed points and anastomoses. The GCL slab enhanced visualization of the capillary-free zones around the arteries and arterioles and helped to differentiate arterial and venous systems. The arterioles and venules were linked by capillaries that were arranged in a mesh-like fashion, with multiple arteriolar feed points and anastomoses. Vascular plexuses in the top and bottom of the INL consisted of capillaries in a vortex arrangement. The center of these vortex arrangements was consistent with the venules in the GCL. Conclusions: HR-OCTA can differentiate the four layers of vascular plexuses in the human macula and elucidate their angiographic features.

KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD. Systemic administration of KUS121 prevented or reduced drusen-like lesions and endoplasmic reticulum stress, and then substantially mitigated chorioretinal pathologies with significant preservation of visual function. Additionally, we confirmed that long-term oral administration of KUS121 caused no systemic complications in drusen-affected monkeys. ATP regulation by KUSs may represent a novel strategy in the treatment of drusen and prevention of disease progression in AMD.

Reduction of lipid accumulation rescues Bietti's crystalline dystrophy phenotypes.

Bietti's crystalline dystrophy (BCD) is an intractable and progressive chorioretinal degenerative disease caused by mutations in the CYP4V2 gene, resulting in blindness in most patients. Although we and others have shown that retinal pigment epithelium (RPE) cells are primarily impaired in patients with BCD, the underlying mechanisms of RPE cell damage are still unclear because we lack access to appropriate disease models and to lesion-affected cells from patients with BCD. Here, we generated human RPE cells from induced pluripotent stem cells (iPSCs) derived from patients with BCD carrying a CYP4V2 mutation and successfully established an in vitro model of BCD, i.e., BCD patient-specific iPSC-RPE cells. In this model, RPE cells showed degenerative changes of vacuolated cytoplasm similar to those in postmortem specimens from patients with BCD. BCD iPSC-RPE cells exhibited lysosomal dysfunction and impairment of autophagy flux, followed by cell death. Lipidomic analyses revealed the accumulation of glucosylceramide and free cholesterol in BCD-affected cells. Notably, we found that reducing free cholesterol by cyclodextrins or δ-tocopherol in RPE cells rescued BCD phenotypes, whereas glucosylceramide reduction did not affect the BCD phenotype. Our data provide evidence that reducing intracellular free cholesterol may have therapeutic efficacy in patients with BCD.

EVALUATION OF MACULAR ISCHEMIA IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION: An Optical Coherence Tomography Angiography Study.

PURPOSE: To quantitatively assess macular perfusion status using optical coherence tomography angiography in eyes with aflibercept-treated central retinal vein occlusion and resolved macular edema and to investigate the impact of macular morphology and perfusion status on visual function. METHODS: This prospective consecutive case series included 23 patients with central retinal vein occlusion. All patients received intravitreal aflibercept injections before analysis. Visual acuity, macular sensitivity, and the macular nonperfusion area (NPA) were evaluated in eyes without macular edema. The macular NPA was evaluated by optical coherence tomography angiography using 3 mm × 3 mm images of the macula. Foveal ellipsoid zone disruption was also analyzed. RESULTS: The superficial macular NPA measured 4.15 mm ± 0.71 mm (95% confidence interval 3.85-4.46), and the deep macular NPA measured 4.23 mm ± 0.97 mm (95% confidence interval 3.82-4.56). The logarithm of the minimum angle of resolution visual acuity was significantly associated with foveal ellipsoid zone disruption (P = 0.001), the superficial macular NPA (P = 0.015), and the deep macular NPA (P = 0.018). Macular sensitivity correlated negatively with logarithm of the minimum angle of resolution visual acuity (P = 0.007), the superficial macular NPA (P = 0.029), and the deep macular NPA (P = 0.040), but not with the foveal ellipsoid zone disruption (P = 0.435). CONCLUSION: Optical coherence tomography angiography is a novel technique that enables segmented evaluation of the macular perfusion status in eyes with central retinal vein occlusion and provides visual prognostic information. Enlargement of the macular NPA in the superficial and deep layers was significantly correlated with impaired visual acuity and with decreased macular sensitivity in patients with aflibercept-treated central retinal vein occlusion and resolved macular edema.

Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema following Central Retinal Vein Occlusion: 1 Initial Injection versus 3 Monthly Injections.

PURPOSE: To compare the 12-month efficacy of 1 initial intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent followed by pro re nata (PRN) dosing with that of 3 initial monthly injections followed by PRN dosing in patients with macular edema (ME) after central retinal vein occlusion (CRVO). METHODS: Twenty-nine eyes received 1 initial injection (1+PRN group) and 20 received 3 monthly injections (3+PRN group). RESULTS: At month 12, changes in logMAR visual acuity from baseline were -0.172 ± 0.372 and -0.142 ± 0.317 in the 1+PRN and 3+PRN groups, respectively; the difference was not significant (p = 0.769). The number of anti-VEGF injections administered in the 3+PRN group (5.9 ± 2.1) was significantly greater than that in the 1+PRN group (4.1 ± 2.8; p = 0.022). CONCLUSION: When used for ME after CRVO, a 1+PRN regimen achieved 12-month outcomes similar to those of a 3+PRN regimen with fewer injections.

EVALUATION OF MACULAR ISCHEMIA IN EYES WITH BRANCH RETINAL VEIN OCCLUSION: An Optical Coherence Tomography Angiography Study.

PURPOSE: To quantitatively assess macular morphology and perfusion status using optical coherence tomography, and optical coherence tomography angiography in eyes with branch retinal vein occlusion when macular edema has completely resolved, and to investigate the impact on visual function. METHODS: Thirty consecutive eyes with branch retinal vein occlusion-macular edema that resolved after treatment with intravitreal ranibizumab injections were included. Macular sensitivity was measured by microperimetry; defect length of foveal ellipsoid zone band was measured using optical coherence tomography; foveal avascular zone and parafoveal nonperfusion areas (NPA) were measured by optical coherence tomography angiography. RESULTS: The logarithm of minimum angle of resolution visual acuity was significantly associated with the defect length of the foveal ellipsoid zone band (P = 0.005), the parafoveal NPA in the superficial capillary plexus (P = 0.007), and the parafoveal NPA in the deep capillary plexus (P = 0.006). Macular sensitivity correlated with parafoveal thickness on the affected side (P = 0.034), the defect length of the foveal ellipsoid zone band (P = 0.048), parafoveal NPA in the superficial capillary plexus (P = 0.008), and parafoveal NPA in the deep capillary plexus (P = 0.012). Multivariate analysis where the only significant parameters in the univariate analyses were used as the independent variables showed that parafoveal NPA was most significantly associated with the logarithm of minimum angle of resolution visual acuity (ß = 0.500, P = 0.005) and macular sensitivity (ß = -0.480, P = 0.007). CONCLUSION: In eyes with branch retinal vein occlusion-macular edema resolved by intravitreal ranibizumab treatments, visual function was strongly associated with parafoveal NPA size.

Morphologic and Functional Retinal Vessel Changes in Branch Retinal Vein Occlusion: An Optical Coherence Tomography Angiography Study.

PURPOSE: The present study aimed to investigate the morphology of the retinal vasculature in eyes with branch retinal vein occlusion (BRVO) using optical coherence tomography (OCT) angiography. DESIGN: Observational case series. METHODS: Fluorescein angiography (FA) and OCT angiography were used to examine macular area and the retinal vasculature at the affected arteriovenous (AV) crossing in 46 patients with BRVO. RESULTS: FA revealed that the affected AV crossing pattern involved arterial overcrossing in 23 eyes (50.0%) and venous overcrossing in 11 eyes (23.9%). However, FA failed to detect the crossing pattern in 10 eyes (21.7%). OCT angiography was significantly more effective for identification of the AV crossing pattern than FA (44 eyes; 95.7%; P = .013). The number of eyes with venous overcrossing detected via OCT angiography (20 eyes, 43.5%) was also higher than that detected via FA (P = .047). OCT angiography revealed that venous narrowing (25.5 ± 21.1 µm) was significantly greater in instances of venous overcrossing than in those of arterial overcrossing (46.4 ± 23.7 µm, P = .005). Macular nonperfusion areas (NPAs) were larger in eyes with venous overcrossing than in those with arterial overcrossing (P = .011 for superficial plexus, P = .049 for deep plexus). The peripheral NPA was significantly larger in eyes with venous overcrossing (65.1 ± 35.3 disc area [DA]) than in those with arterial overcrossing (17.2 ± 24.1 DA; P < .001). CONCLUSIONS: Our findings suggest that BRVO characterized by venous overcrossing may be more prevalent than previously reported, and that there is a significant association between NPA size and AV crossing pattern.

Retinal Blood Flow Velocity Change in Parafoveal Capillary after Topical Tafluprost Treatment in Eyes with Primary Open-angle Glaucoma.

Although ocular circulation at the retina and optic disc is known to be associated with the pathology of glaucoma, direct measurement of blood flow velocity has been difficult to obtain. This prospective observational study enrolled 11 consecutive patients with treatment-naïve primary open-angle glaucoma (POAG) and 11 healthy subjects, and the effects of topical tafluprost treatment on ocular circulation were examined at baseline and at 1, 4, and 12 weeks after initiating treatment with topical tafluprost on POAG patients using multiple modalities, which include adaptive optics scanning laser ophthalmoscopy (AOSLO). Baseline mean intraocular pressure (IOP) was significantly higher and mean parafoveal blood flow velocity (pBFV) was significantly lower in POAG eyes than in healthy eyes. Mean IOP was significantly decreased (1 week, -19.1%; 4 weeks, -17.7%; and 12 weeks, -23.5%; all P < 0.001) and mean pBFV was significantly increased from the baseline at all follow-up periods after initiating treatment (1 week, 14.9%, P = 0.007; 4 weeks, 21.3%, P < 0.001; and 12 weeks, 14.3%, P = 0.002). These results reveal that tafluprost may not only lower IOP but may also improve retinal circulation in POAG eyes and AOSLO may be useful to evaluate retinal circulatory change after treatment.

Association of Glaucoma-Susceptible Genes to Regional Circumpapillary Retinal Nerve Fiber Layer Thickness and Visual Field Defects.

Purpose: To examine the associations of the earlier reported glaucoma-related genes to the regional circumpapillary retinal nerve fiber layer thicknesses (cpRNFLTs) and corresponding visual field defects. Methods: We studied 756 patients with primary open-angle glaucoma (POAG) and 3094 normal controls. Each participant was genotyped for nine single nucleotide polymorphisms (SNPs) of four glaucoma-susceptible genes: the CDKN2B(AS1), TMCO1, CAV1/CAV2, and SIX1/SIX6 genes. For the SNPs that were significantly associated with the POAG case-control analyses, the associations of SNP genotypes with the cpRNFLTs of 12 sectors were also analyzed, and then finer assessments were performed using 768 points of the cpRNFLT and corresponding visual field defect sensitivities using case-only subjects. Results: We confirmed that there was a significant association of the CDKN2B(AS1) gene to POAG. For the suggested region-specific associations of these genes with the 12-sectored cpRNFLT, a 768-point cpRNFLT examination showed that rs4977756 near CDKN2B had significant signal peaks in the temporal region at 330° to 360° and 0° to 30° (maximum ß = 2.92, P = 2.9 × 10-5 at 351.1° and maximum ß = 3.97, P = 2.2 × 10-4 at 23.4°, respectively). These region-specific signals were validated by the corresponding visual field defect patterns of the paracentral/lower hemifield (P < 0.05). Conclusions: Genetic association analyses using the cpRNFLT with 768 points suggest that the CDKN2B gene was associated with paracentral/lower hemifield scotomas. Our regional association analyses on cpRNFLT allow detailed characterization of glaucoma-related genes and should be a new target for genomic studies for glaucoma endophenotypes.

Longitudinal change in choroidal thickness after trabeculectomy in primary open-angle glaucoma patients.

PURPOSE: To investigate longitudinal changes in intraocular pressure (IOP), axial length (AL), and choroidal thickness (ChT) in primary open-angle glaucoma (POAG) eyes after trabeculectomy and to evaluate the parameters that might influence those changes. METHODS: In this prospective observational study, we recruited 28 patients with POAG (28 eyes) scheduled for trabeculectomy. The average macular ChTs and foveal retinal thicknesses along 6-mm segments centered on the fovea were examined preoperatively and postoperatively (at 1, 3, and 6 months) using swept-source optical coherence tomography. The IOP, AL, and mean deviation (MD) of standard automated perimetry (SAP) were also analyzed as independent variables. RESULTS: Results from 16 patients were included in the final analysis. A significant increase in ChT with respect to the preoperative value was observed at every postoperative stage (1 month, P < 0.001; 3 months, P < 0.001; 6 months, P = 0.011), whereas the retinal thickness showed no significant change over the study period. The ChT increase and IOP reduction were sustained throughout the 6-month period without further significant changes. Stepwise multivariate analyses showed significant correlations between the percentage decrease in IOP and the percentage increase in ChT at 1 and 6 months postoperatively. The percentage increase in ChT was also significantly correlated with a better MD of the SAP at 1 month (ß = 0.01; P = 0.009). CONCLUSIONS: The ChT increase following trabeculectomy was sustained at 1, 3, and 6 months postoperatively. The percentage increase in ChT was significantly correlated with the percentage change in IOP and (more weakly) with better SAP MD values.

ASSOCIATIONS BETWEEN MACULAR EDEMA AND CIRCULATORY STATUS IN EYES WITH RETINAL VEIN OCCLUSION: An Adaptive Optics Scanning Laser Ophthalmoscopy Study.

PURPOSE: To investigate associations between parafoveal microcirculatory status and foveal pathomorphology in eyes with macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS: Ten consecutive patients (10 eyes) with acute retinal vein occlusion were enrolled, 9 eyes of which received intravitreal ranibizumab (IVR) injections. Foveal morphologic changes were examined via optical coherence tomography (OCT), and parafoveal circulatory status was assessed via adaptive optics scanning laser ophthalmoscopy (AO-SLO). RESULTS: The mean parafoveal aggregated erythrocyte velocity (AEV) measured by adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion was 0.99 ± 0.43 mm/second at baseline, which was significantly lower than that of age-matched healthy subjects (1.41 ± 0.28 mm/second, P = 0.042). The longitudinal adaptive optics scanning laser ophthalmoscopy examinations of each patient showed that parafoveal AEV was strongly inversely correlated with optical coherence tomography-measured central foveal thickness (CFT) over the entire observation period. Using parafoveal AEV and central foveal thickness measurements obtained at the first and second examinations, we investigated associations between differences in parafoveal AEV and central foveal thickness, which were significantly and highly correlated (r = -0.84, P = 0.002). CONCLUSION: Using adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion macular edema, we could quantitatively evaluate the parafoveal AEV. A reduction or an increase in parafoveal AEV may be a clinical marker for the resolution or development/progression of macular edema respectively.

RANIBIZUMAB FOR MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION: One Initial Injection Versus Three Monthly Injections.

PURPOSE: To compare the 12-month-efficacy of 1 initial intravitreal ranibizumab injection (IVR) followed by pro re nata (PRN) dosing with that of three initial monthly IVR followed by PRN dosing in patients with macular edema (ME) after branch retinal vein occlusion. DESIGN: Prospective, interventional study. METHODS: Of 81 eyes, 42 received 1 initial IVR injection (1+PRN group) and 39 eyes received 3 monthly IVRs (3+PRN). Pro re nata injections were performed when fovea exudative changes were evident. RESULTS: At Month 12, the visual acuity (VA) changes from baseline were -0.245 ± 0.227 and -0.287 ± 0.222, in the 1+PRN and 3+PRN groups, respectively; there were no significant difference between groups (P = 0.728). The stratified analysis showed that patients with better VA (baseline VA >20/40) had similar significant improvement in VA at Month 12 (P < 0.001) to that of those with poorer VA (≤20/40). Better VA at Month 12 was significantly associated with younger age, better baseline VA, and thinner baseline central foveal thickness (P = 0.003, < 0.001, and < 0.001, respectively). Mean total number of IVR injections in the 1+PRN and 3+PRN groups were 3.8 ± 1.8 and 4.6 ± 1.4, respectively (P = 0.060). In both groups, shorter durations to the first PRN injection were associated with greater total PRN injection number (1+PRN, P = 0.006; 3+PRN; group, P < 0.001). CONCLUSION: In IVR treatment for ME after branch retinal vein occlusion, 1+PRN and 3+PRN regimens achieved similar 12-month functional outcomes. Patients with shorter durations to initial PRN injection may require more PRN treatments.

ASSOCIATION BETWEEN RETINAL HEMORRHAGIC PATTERNS AND PERFUSION STATUS IN EYES WITH ACUTE CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To evaluate peripheral retinal hemorrhagic patterns in eyes with acute central retinal vein occlusion, and to explore their clinical relevance in differentiating for the retinal perfusion status, through a prospective, and cross-sectional study. METHODS: Fifty eyes with acute central retinal vein occlusion were included. Retinal hemorrhagic patterns at the equator and retinal perfusion status were evaluated by ultra-wide field fundus photography and fluorescein angiography. RESULTS: Retinal perfusion was categorized as nonischemic in 29 eyes, ischemic in 18 eyes, and undeterminable in 3 eyes. None of the examined eyes had flame-shaped retinal hemorrhages in the periphery. All hemorrhages were rounded-dot or blot and were variable in size. Particle analysis was performed to quantify hemorrhage size, and showed higher values in eyes having larger blot hemorrhages, and lower values in eyes having dot or smaller blot hemorrhages. Mean size of maximum peripheral dot or blot hemorrhage was larger in eyes classified as ischemic (10,763.0 ± 5,946.3 pixels) than as nonischemic (2,839.9 ± 1,153.6 pixels, P < 0.001). The authors calculated area under the curve to investigate the ability of continuous variables to discriminate retinal perfusion status, which was 0.963 (P < 0.001) for mean size of maximum peripheral blot hemorrhages. CONCLUSION: The authors objectively evaluated retinal hemorrhagic patterns at the equator in eyes with acute central retinal vein occlusion using particle analysis. The resulting hemorrhage size measurement was considered to be often useful in determining retinal perfusion status. Because they can be noninvasively evaluated with readily available equipment, peripheral hemorrhagic patterns might be good clinical markers of retinal perfusion.

Association between retinal hemorrhagic pattern and macular perfusion status in eyes with acute branch retinal vein occlusion.

This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28, and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P < 0.001). Parallelism in eyes with a flame-shaped hemorrhage was higher than in those with a non-flame-shaped hemorrhage (P < 0.001), and in those with a nonischemic macula versus those with an ischemic macula (P < 0.001). The area under the curve for parallelism was 0.975 (P < 0.001), suggesting an accurate diagnostic parameter for macular perfusion differentiation. In conclusion, we objectively evaluated retinal hemorrhagic patterns at the posterior pole in BRVO using the parallelism method, which was useful in differentiating macular perfusion status.