Intraocular pressure changes during intravitreal aflibercept injection based on treat-and-extend regimen in Japanese patients with neovascular age-related macular degeneration and glaucoma.

PURPOSE: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2 mg/0.05 ml of aflibercept and followed for 52 weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52 weeks were recorded. RESULTS: The mean of aflibercept injections was 8.3 ± 1.9. The mean IOP at baseline was 14.0 ± 3.1 mmHg, and the mean IOP after aflibercept therapy was 13.0 ± 2.4 mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery. CONCLUSION: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma.

Complement activation products in tears of dry eye and meibomian gland dysfunction.

Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.

Tear fluid and complement activation products in tears after ocular surgery.

PURPOSE: Due to technological advancements, surgical invasiveness has been reduced. However, cataract surgery has been implicated in causing postoperative inflammation, including dry eye syndrome. The innate immune system may be involved in postoperative inflammation, and complement activation could potentially play a crucial role in defense against pathogens, homeostasis, and wound healing. To investigate changes in the tear film complement activation products (CAPs) and ocular surface after vitrectomy combined with cataract surgery. METHODS: Forty-three patients (23 women; median age, 69 years) were enrolled in this prospective study and underwent phacoemulsification and vitrectomy. We measured Schirmer's test (ST) and CAPs in the tears at baseline (the day before surgery), 4 days and 1 month after the surgery. Tears were collected in microtubes. The CAPs in the tear fluid were analyzed by cytometric bead array. RESULTS: The median ST (8.5 mm) at baseline increased to 16 mm at 4 days ( P < 0.001) and 10 mm at 1 month (P = 0.44). The C3a levels (1202 pg/ml) at baseline increased to 2753 pg/ml at 4 days (P < 0.001), and 1763 pg/ml at 1 month (P = 0.049). The C4a levels (476 pg/ml) at baseline increased to 880 pg/ml at 4 days (P < 0.001), and 657 pg/ml at 1 month (P = 0.013). The C5a levels (22.6 pg/ml) at baseline increased to 470.9 pg/ml at 4 days (P < 0.001), and 38.3 pg/ml at 1 month (P = 0.0048). The surgical eyes were divided into the short ST group (≦ 10 mm, n = 22) and long ST group (> 10 mm, n = 21) based on the preoperative ST values. At 1 month postoperatively, the C3a levels were 2194 pg/ml in the preoperative short ST group and 1391 pg/ml in the long ST group, with significantly higher C3a concentrations in the short ST group (P < 0.001). CONCLUSIONS: The CAPs levels in tears increased after vitrectomy combined with cataract surgery. A preoperative deficit in tear secretion might induce prolonged complement activation and delayed recovery of ocular surface parameters postoperatively.

MACULAR SENSITIVITY CHANGE AFTER COMPLEMENTARY LASER THERAPY AFTER RANIBIZUMAB INTRAVITREAL INJECTION IN BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: We examined the effect of ranibizumab with or without laser photocoagulation on retinal sensitivity in eyes with branch retinal vein occlusion. METHODS: Prospective randomized control study. Thirty patients with branch retinal vein occlusion received intravitreal injection of ranibizumab in a monthly pro re nata regimen. Fifteen patients received ranibizumab monotherapy alone (monotherapy group). The remaining 15 patients received rescue laser therapy at 3 or 9 months (combined group). The retinal sensitivity was measured at 32 points within central 8°, and the average of the main occlusion side among the 16 upper or 16 lower points was defined as the affected area sensitivity. RESULTS: In comparing the monotherapy group and the combined group, the number of injections during the 12 months was 5.4 versus 4.9, the change in retinal thickness ( µ m) was -254 versus -197, the ETDRS letters of improvement was +18.3 versus +19.6, and the change in the affected area sensitivity (dB) was +7.1 versus +4.6. At 12 months, all these results were significantly improved compared with their respective baselines, but none of the differences between the two groups reached statistical significance. CONCLUSION: Retinal sensitivity at 12 months improved in both the monotherapy group and the combined group. The additional laser did not reduce the number of injections or further improve visual acuity nor did it affect retinal sensitivity.

Age-Related Maculopathy Susceptibility 2 and Complement Factor H Polymorphism and Intraocular Complement Activation in Neovascular Age-Related Macular Degeneration.

Purpose: To investigate the association of risk alleles in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) with complement activation products in the aqueous humor in eyes with neovascular age-related macular degeneration (nAMD) including polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and pachychoroid neovasculopathy (PNV). Design: Prospective, comparative, observational study. Participants: Treatment-naïve patients with nAMD and cataract patients as controls. Methods: The study included 236 eyes of 236 patients with nAMD and 49 control eyes of 49 patients. Aqueous humor samples were collected from 67 eyes with drusen-associated nAMD, 72 eyes with PCV, 26 eyes with RAP, and 71 eyes with PNV before intravitreal anti-VEGF injection and cataract surgery in the 49 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, and C5a using a bead-based immunoassay. Genotyping of the ARMS2 A69S (rs10490924), CFH I62V (rs800292), and CFH Y402H (rs1061170) was performed using TaqMan genotyping. Main Outcome Measures: The levels of complement activation products (C3a, C4a, and C5a) in the aqueous humor in each genotype of ARMS2 and CFH. Results: The C3a level in the aqueous humor was significantly elevated (P = 0.006) in patients with nAMD and the ARMS2 A69S risk allele, whereas the levels of the complement activation products were not associated with CFH I62V and Y402H genotypes. Among the control eyes, no significant differences were seen in any complement activation products for all genetic polymorphisms. The levels of the complement activation products in the aqueous humor of eyes with the nAMD subtypes for each genetic polymorphism did not show significant differences. Conclusions: The C3a concentration in the aqueous humor was significantly higher in Japanese nAMD patients with the ARMS2 A69S risk allele, whereas it was not elevated in the patients with CFH I62V. Age-related maculopathy susceptibility 2 A69S polymorphism is strongly associated with local complement activation in nAMD patients.

Morphometrics in three dimensional choroidal vessel models constructed from swept-source optical coherence tomography images.

We created three types of vessel models: vessel volume, surface, and line models from swept-source optical coherence tomography images and tested experimentally calculated three-dimensional (3D) biomarkers. The choroidal volume (CVolume), surface area (VSurface), and vessel length-associated index (VLI) were measured. The calculated 3D parameters were the mean choroidal thickness, choroidal vascularity index (CVI), vessel length density index (VLDI), vessel length to the stromal (VL-S) ratio, surface-to-volume ratio (S-V ratio), and vessel diameter index (VDI). Cluster analysis showed that the parameters were classified into two clusters: one was represented by the VVolume including the CVolume, VSurface, CVI, S-V ratio, VLI, VDI, and subfoveal choroidal thickness and the other by the VL-S ratio including the VLDI. Regarding the regional distribution, the VVolume, CVolume, VSurface, CVI, VLI, VL-S ratio, and VDI at the foveal center were higher than at the parafovea (P < 0.01). Although the VVolume decreased with age and axial length (AL) elongation, the association of the 3D parameters with age and AL elongation differed. The VLI, VLDI, VL-S ratio, and CVI decreased with age (P < 0.01) but not with AL elongation. The results suggested a structural difference in the choroidal vessel volume reduction between aging and AL elongation. The 3D parameters may provide additional information about the choroidal vasculature.

Short-term results for brolucizumab in treatment-naïve neovascular age-related macular degeneration: a Japanese multicenter study.

PURPOSE: To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study. STUDY DESIGN: Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated. RESULTS: Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P < 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases. CONCLUSIONS: IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.

The characteristics of choriocapillaris flow void in the unilateral polypoidal choroidal vasculopathy fellow eyes.

To evaluate the morphological characteristics of flow void (FV) in the fellow eyes of the unilateral polypoidal choroidal vasculopathy (PCV). Fifty PCV fellow eyes (PCVF) and 31 age-matched normal ocular circulation controls were recruited in this retrospective study. The number of FV was analyzed according to the size in a centered 5 × 5 mm swept source optical coherence tomography angiography scans. We used indocyanine green angiography images to determine whether choroidal vascular hyperpermeability (CVH) has occurred. For the PCVF, the prevalence rate of CVH was 70% (35 of 50) The number of FVs was significantly lower in 400-25,000 µm2 (P = 0.005), 400-500 µm2 (P = 0.001), 525-625 µm2 (P = 0.001) and 650-750 µm2 (P = 0.018). compared to the controls. And showed no difference in size from 775 to 1125 µm2 between the two groups. The area under the receiver operating characteristic curve of PCVF with CVH and controls was 0.94 (95% CI 0.88-1.00) (P < 0.001). We found that the number of small FVs was significantly lower in the PCV fellow eyes than that in the eyes with control group.

A modified measuring method to investigate the choriocapillaris flow void of polypoidal choroidal vasculopathy with swept source optical coherence tomography angiography.

BACKGROUND: To propose a modified method to investigate the flow void of polypoidal choroidal vasculopathy (PCV) choriocapillaris. METHODS: This paper involves a retrospective study. Included 30 PCV affect eyes, 30 old control eyes, 20 young control eyes, 15 affect eyes with anti-VEGF intravitreal injection treatment, and 8 fellow eyes of anti-VEGF intravitreal injection treatment group. After the choriocapillaris slab [10 µm thick starting 30 µm beneath to the retinal pigment epithelium (RPE)-fit reference] was extracted from macular optical coherence tomography angiography 6×6-mm scans, the flow void was segmented by the Phansalkar method. We analyzed the flow void sizes-frequency histogram in order to investigate the differences of flow void proportion between groups. Then we verified the differences between groups after anti-VEGF intravitreal injection treatment. RESULTS: On the difference curve between the PCV group and Old control group, there was a peak appeared at the flow void sizes range from 900 to 1,125 µm2. The average number of flow void sizes from 900 to 1,125 µm2 was significantly higher in the Old control group than that in the Young control group (P<0.05) and there was no difference between the affect eyes group and the Old control group. The proportion of flow void sizes from 900 to 1,125 µm2 were remarkably higher in the affect eyes group compared to the Old control group (P<0.05), showing no difference between the Young control group and the Old control group. The average number of flow void sizes from 900 to 1,125 µm2 and the proportion of flow void sizes range from 900 to 1,125 µm2 were significantly higher in the treatment group after the treatment (P<0.05) and there was no difference in the fellow eyes of treatment group. The choroidal thickness was significantly reduced after the treatment of the treatment group (P<0.001), while the fellow eyes of the treatment group had no difference. CONCLUSIONS: Our method was specific for the pathological changes in choriocapillaris structures of PCV affect eyes, fellow eyes, and the affect eyes after anti-VEGF treatment.

Changes in complement activation products after anti-VEGF injection for choroidal neovascularization in age-related macular degeneration and pachychoroid disease.

We evaluated changes in the complement system resulting from anti-vascular endothelial growth factor (VEGF) in eyes with age-related choroidal neovascularization (CNV) including neovascular age-related macular degeneration, pachychoroid neovasculopathy, and polypoidal choroidal neovasculopathy. We measured the concentrations of the complement activation products (C3a, C4a), VEGF, and monocyte chemotactic protein-1 in the aqueous humor during intravitreal anti-VEGF injections for CNV. The VEGF level decreased significantly (P < 0.001), while the C3a and C4a levels increased significantly (P < 0.001 for both comparisons) 1 month after two monthly anti-VEGF injections. The VEGF level was correlated with the C3a (R = 0.328, P = 0.007) and C4a (R = - 0.237, P = 0.055) levels at baseline, but the correlation between the VEGF and C3a levels (R = - 0.148, P = 0.242) changed significantly (P = 0.028 by analysis of covariance) after anti-VEGF treatment. The C3a increase after anti-VEGF therapy did not change the visual outcomes in eyes with CNV for 1 year. Dysregulation of the complement system can be induced after anti-VEGF therapy.

Complement Activation Products and Cytokines in Pachychoroid Neovasculopathy and Neovascular Age-Related Macular Degeneration.

Purpose: To investigate the characteristics of complement activation products and angiogenic cytokines in the aqueous humor in eyes with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD). Methods: This was a prospective, comparative, observational study. All patients with choroidal neovascularization were classified as PNV without polyps, PNV with polyps (polypoidal choroidal vasculopathy [PCV]), or drusen-associated nAMD according to the presence or absence of pachychoroid features and soft drusen. This study included a total of 105 eyes. Aqueous humor samples were collected from 25 eyes with PNV without polyps, 23 eyes with PCV, and 24 eyes with drusen-associated nAMD before intravitreal anti-vascular endothelial growth factor (VEGF) injection and cataract surgery in 33 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, C5a, VEGF, and macrophage chemoattractant protein 1 (MCP-1) using a bead-based immunoassay. Results: C3a and MCP-1 levels were significantly higher in PCV (P = 0.032 and P = 0.039, respectively) and drusen-associated nAMD (P = 0.01 for both comparisons) than in controls, and no difference was seen in C3a and MCP-1 levels between PNV and controls (P = 0.747 and P = 0.294, respectively). VEGF levels were significantly higher in PNV (P = 0.016), PCV (P = 0.009), and drusen-associated nAMD (P = 0.043) than in controls. In PNV, the VEGF levels elevated without elevated C3a and MCP-1. Conclusions: PNV, PCV, and drusen-associated nAMD had significantly distinct profiles of complement activation products and cytokines in the aqueous humor.

Three-year outcome of aflibercept treatment for Japanese patients with neovascular age-related macular degeneration.

BACKGROUND: To evaluate the three-year outcome after intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD). METHODS: Forty-nine treatment-naïve nAMD patients (50 eyes) were enrolled in this prospective study. The eyes received IAI at two-month intervals in the first year. The treatment regimen was changed to IAI based on a treat-and-extend approach in the second and third years. RESULTS: Twenty-nine eyes of 28 patients were successfully followed up over 36 months. The nAMD subtypes included 15 eyes with typical AMD and 14 eyes with polypoidal choroidal vasculopathy. The number of IAIs performed over the 3 years was 17.2 ± 3.1 (mean ± standard deviation). The mean logMAR, which was 0.42 at baseline, improved to 0.19 (P = 0.001) at 12 months, and 0.26 (P = 0.049) at 36 months. The central retinal thickness (CRT) was 329 ± 120 µm at baseline, 151 ± 38 µm (P < 0.001) at 12 months, and 143 ± 61 µm (P < 0.001) at 36 months. The mean subfoveal choroidal thickness (SFCT) was 288 ± 97 µm at baseline, 243 ± 82 µm (P < 0.001) at 12 months, and 208 ± 63 µm (P < 0.01) at 36 months. The changes in logMAR, CRT, and SFCT over the study period did not differ between typical AMD and PCV. CONCLUSION: Long-term aflibercept injection can achieve visual improvement and reduce the thickness of the retina and choroid in nAMD. Morphological improvement of these tissues may not be sufficient to sustain earlier visual improvement over the long-term.

Semantic Segmentation of the Choroid in Swept Source Optical Coherence Tomography Images for Volumetrics.

The choroid is a complex vascular tissue that is covered with the retinal pigment epithelium. Ultra high speed swept source optical coherence tomography (SS-OCT) provides us with high-resolution cube scan images of the choroid. Robust segmentation techniques are required to reconstruct choroidal volume using SS-OCT images. For automated segmentation, the delineation of the choroidal-scleral (C-S) boundary is key to accurate segmentation. Low contrast of the boundary, scleral canals formed by the vessel and the nerve, and the posterior stromal layer, may cause segmentation errors. Semantic segmentation is one of the applications of deep learning used to classify the parts of images related to the meanings of the subjects. We applied semantic segmentation to choroidal segmentation and measured the volume of the choroid. The measurement results were validated through comparison with those of other segmentation methods. As a result, semantic segmentation was able to segment the C-S boundary and choroidal volume adequately.

Evidence for Activation of Lectin and Classical Pathway Complement Components in Aqueous Humor of Neovascular Age-Related Macular Degeneration.

PURPOSE: The complement system is activated via 3 different pathways; the lectin pathway (LP), classical pathway (CP), and alternative pathway. To investigate the possible roles for the LP or CP in the development of neovascular age-related macular degeneration (nAMD), we compared aqueous humor levels of complement proteins of the LP and CP between eyes with nAMD and those with cataract as controls. METHODS: Seventeen eyes from 17 patients with treatment-naïve nAMD and 9 eyes from 9 patients with cataract were studied. Aqueous humor samples were collected before intravitreal aflibercept or ranibizumab injection for the nAMD patients and before cataract surgery for the cataract patients. Aqueous humor levels of complement C4 of the LP and CP, complement C3 of all 3 complement pathways, and mannose-binding lectin-associated serine protease (MASP)-2 of the LP were measured by enzyme-linked immunosorbent assay. Aqueous humor levels of C4a and C3a, the activation products of C4 and C3, respectively, were measured by a bead-based immunoassay. The ratios of C4a to C4 and C3a to C3, representing the degree of C4 and C3 activation, respectively, were calculated in individual patients. RESULTS: The aqueous humor levels of C4, C3, and MASP-2 were significantly lower in the nAMD eyes compared to the controls (p = 0.008, p = 0.011, and p = 0.018, respectively). In contrast, the aqueous humor levels of C4a and C3a, as well as the C4a/C4 and C3a/C3 ratios, were significantly higher in the nAMD eyes compared to the controls (p = 0.039, p = 0.003, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: This study provides evidence for significant intraocular activation of either or both of the LP and CP in nAMD eyes that might be involved in the development of nAMD. The significantly lower levels of MASP-2 in the aqueous humor of the nAMD eyes were likely due to MASP-2 consumption by activation of the LP.

Bilateral Serous Retinal Detachment Associated with Inferior Posterior Staphyloma Treated with Scleral Shortening and Vitrectomy.

PURPOSE: We report a case of bilateral serous retinal detachment (SRD) associated with inferior posterior staphyloma (IPS) treated successfully with scleral shortening. PATIENT AND METHODS: A 63-year-old woman presented with bilateral visual loss due to an SRD with IPS. The best-corrected visual acuity levels were 0.6 (20/30) and 0.5 (20/40) in the right and left eye, respectively. The patient underwent vitrectomy and scleral shortening in the right eye. The lamellar scleral crescent was resected 4 mm in width from the 5- to 8-o'clock positions. Seven interrupted 5-0 polyester sutures were placed at the edge of the lamellar scleral crescent. After 25-gauge three-port vitrectomy, the sutures were tightened. Optical coherence tomography showed decreased curvature at the staphyloma border. The choroidal thickness decreased in the superior flat portion of the fundus and increased slightly in the staphyloma. The SRD resolved 3 months postoperatively. The best-corrected visual acuity in the right eye improved to 0.8 (20/25) 6 months postoperatively. Angiography 6 months postoperatively showed decreased diffuse dye leakage at the fovea in the right eye; indocyanine green angiography did not show marked changes. DISCUSSION: Scleral shortening with vitrectomy changes the eye wall shape, may improve the retinal pigment epithelial integrity, and may be a treatment option for SRD with IPS.

Multimodal Imaging of a Case of Acute Annular Outer Retinopathy.

Background: Acute annular retinopathy (AAOR) is a rare entity showing grayish spots with annular lesions. We report the clinical characteristics of a patient with AAOR derived by using multimodal imaging including spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF), and an adaptive optics fundus camera. Case: A 56-year-old man who had fever one month and a half before presenting. He noticed bilateral visual loss after lowering of fever. Clinical findings: Grayish white rings of different sizes were seen in the posterior fundus. Margin of the lesion showed hyperautofluorescence. OCT demonstrated an indistinct ellipsoid zone, disruption of external limiting membrane, and bulging of the retinal pigment epithelium in the annular lesions. We found hyperreflective foci in the inner retina and an indistinct interdigitation zone on the OCT images and indistinct cone mosaic patterns on the AO images at an ophthalmoscopically normal fovea in the left eye. Conclusion: Multimodal imaging showed the damage in the photoreceptors and the retinal pigment epithelium at the annular lesions. OCT and AO imaging can demonstrate abnormal findings in ophthalmoscopically normal areas in eyes with AAOR.

Morphologic changes of the fovea and visual acuity associated with retinal detachment secondary to circumscribed choroidal hemangioma.

PURPOSE: To clarify and review the early and late morphologic changes of the macula associating with visual loss in patients with subfoveal fluid secondary to extrafoveal circumscribed choroidal hemangiomas. METHODS: Previously six non-treated eyes of six patients with subfoveal retinal detachment secondary to extrafoveal circumscribed choroidal hemangioma were included. Visual acuity (VA), duration of visual symptoms, color fundus photography, optical coherence tomography (OCT), fundus autofluorescence, and fluorescein angiography (FA) were evaluated. RESULTS: The mean patient age was 58 years (range, 25-78). The VA and duration of symptoms in each patient was 1.2 (3 days), 0.6 (1 week), 0.4 (3 months), 0.5 (6 months), 0.02 (12 months), and 0.01 (8 years), respectively. Three patients with symptoms for less than 3 months did not have retinal pigment epithelial (RPE) alterations, retinal edema, or thinning of the retinal structure in the fovea. A patient with symptoms for 3 months had subfoveal deposits underneath the detached neurosensory retina with foveal hyperautofluorescence. Two patients with symptoms exceeding 12 months had highly affected RPE and cystoid macular degeneration. CONCLUSIONS: The VA was affected in patients with longer visual symptoms, and there are some changes in the retina and RPE in the fovea by FA and OCT. Persistent subretinal fluid secondary to choroidal hemangiomas may result in pathologic changes in the neurosensory retina.

Analysis of the feed-forward effects of sink activity on the photosynthetic source-sink balance in single-rooted sweet potato leaves. I. Activation of RuBPcase through the development of sinks.

Single-rooted sweet potato leaves having a petiole with a fragment of stem allocated exceptionally large amounts of photosynthates to tuberous roots, the only major storage organ, throughout an experimental period of 50 d. The increase in photosynthetic activity for CO(2) fixation depended exclusively on the development of sink activity due to the growth of tuberous roots. Thus this model expressed a remarkable feed-forward effect on the photosynthetic source-sink balance. The level of ribulose-1,5-bisphosphate carboxylase (RuBPcase) protein in the leaves increased continuously during the period. The lowered initial as well as total activity of RuBPcase observed at the start of the experiment was raised with the cancellation of the sink-limited state due to the development of tuberous roots. The maximum activity determined after removing some inhibitor(s) from the enzyme by treating the leaf extract with SO(4)(2-) was much greater than the total activity and remained approximately constant throughout the experimental period. The clear decrease in the difference between maximum and total activities with the development of tuberous roots might reflect the reactivation of RuBPcase due to the removal of some inhibitor(s) from the enzyme through the cancellation of the sink-limited state.