One-Year Outcomes of 1 + pro re nata versus 3 + pro re nata Intravitreal Aflibercept Injection for Neovascular Age-Related Macular Degeneration.

PURPOSE: We compared 1-year outcomes of 1 + pro re nata (PRN) versus 3 + PRN of intravitreal aflibercept injection (IAI) for age-related macular degeneration (AMD). METHODS: Forty-two eyes with naïve AMD received 3 + PRN IAI treatment and 47 eyes with naïve AMD received 1 + PRN IAI treatment. Visual acuity (VA), central retinal thickness (CRT), and central choroidal thickness (CCT) and number of administered IAIs during 12 months were compared. RESULTS: VAs improved, and CRTs reduced significantly at any given month from baseline in both groups (p < 0.01, respectively). CCT reduced significantly at 3 months in the 3 + PRN group (p = 0.024) but not in the 1 + PRN group. The 1 + PRN group received fewer injections than the 3 + PRN group (p < 0.01). CONCLUSIONS: Aflibercept leads to equivalent VA and morphologic retinal improvement without administering 3 injections.

Expression of Vascular Endothelial Growth Factor by Retinal Pigment Epithelial Cells Induced by Amyloid-ß Is Depressed by an Endoplasmic Reticulum Stress Inhibitor.

PURPOSE: Amyloid-ß (Aß) is a 36- to 43-amino-acid peptide that is a constituent of drusen, and it has been demonstrated to upregulate vascular endothelial growth factor (VEGF) expression by retinal pigment epithelial (RPE) cells. This study aimed to determine whether 4-phenylbutyl phosphonylacetate (PBA), a known endoplasmic reticulum (ER) stress inhibitor, can reduce Aß-induced expression of VEGF in RPE cells. METHODS: Aß was added to the medium of regularly cultured or polarized ARPE-19 cells, a human RPE cell line, with or without PBA. The levels of VEGF and ER stress markers, namely GRP78/Bip, cleaved caspases 4 and 12 and GADD153/C-EBP homologous protein, were determined by enzyme-linked immunoassay, immunocytochemistry and Western blotting. RESULTS: Exposure of ARPE-19 cells to Aß induced GRP78/Bip expression and activated caspases 4 and 12; however, their expression was decreased by simultaneous exposure to PBA. Aß increased the expression of VEGF both in regularly cultured and polarized ARPE-19 cells, but it was suppressed by PBA. PBA did not cause RPE cell apoptosis. CONCLUSION: Aß has been suggested to be involved in the development of age-related macular degeneration; therefore, our findings suggest that drugs that target ER stress should be considered for the treatment of age-related macular degeneration.

A Japanese boy with Bardet-Biedl syndrome caused by a novel homozygous variant in the ARL6 gene who was initially diagnosed with retinitis punctata albescens: A case report.

PURPOSE: Bardet-Biedl Syndrome (BBS) is an autosomal recessive systemic disorder characterized by retinitis pigmentosa, polydactyly, obesity, intellectual disability, renal impairments, and hypogonadism. The purpose of this study was to determine the ocular characteristics of a boy with BBS caused by a novel homozygous variant in the ARL6 (alternative named BBS3) gene who had been originally diagnosed with retinitis punctata albescens. METHODS: This was an observational case study. The patient underwent ophthalmological examinations, electroretinography, and genetic analyses using whole-exome sequencing. RESULTS: A 7-year-old boy was examined in our hospital with complaints of a progressive reduction of his visual acuity and night blindness in both eyes. There was no family history of eye diseases and no consanguineous marriage. Fundus examinations showed numerous white spots in the deep retina and retinal pigment epithelium. Fundus autofluorescence showed hypofluorescence consistent with these spots. Both the scotopic and photopic components of the full-field electroretinographies were non-detectable. Based on these clinical findings, this boy was suspected to have retinitis punctata albescens. Subsequent genetic testing using whole-exome sequencing revealed a novel homozygous variants in the ARL6/BBS3 gene (NM_001278293.3:c.528G>A, (p.Trp176Ter)). A systemic examination by the pediatric department revealed that this boy had a history of a surgical excision of polydactyly on his left foot when he was born, and that he was mildly obese. There were no prominent intellectual or gonadal dysfunctions, no craniofacial or dental abnormalities, no congenital heart disease, and no hearing impairment. He was then clinically and genetically diagnosed with BBS. CONCLUSION AND IMPORTANCE: In children with night blindness and progressive visual dysfunction, it is important for ophthalmologists to consult clinical geneticists and pediatricians to rule out the possibility of systemic diseases such as BBS.

Changes in areas of capillary nonperfusion after intravitreal injection of bevacizumab in eyes with branch retinal vein occlusion.

PURPOSE: : To study the effect of an intravitreal bevacizumab (IVB) on the retinal ischemia in eyes with a branch retinal vein occlusion. METHODS: : Fluorescein angiography was performed before and 1 month after the IVB (1.25 mg/0.05 mL) in 58 consecutive eyes of 58 patients with macular edema secondary to a branch retinal vein occlusion. The area of capillary nonperfusion was measured on an early-phase fluorescein angiography image by an area measurement program, and the area was expressed relative to the optic disk area (DA). A blockage of the fluorescence by the retinal hemorrhage was distinguished from nonperfusion by comparisons with retinal photographs. RESULTS: : Thirty-seven of 58 eyes did not have any capillary nonperfusion before the IVB, and capillary nonperfusion developed in 3 of these 37 eyes 1 month after the IVB. The area of nonperfusion in these 3 eyes was 0.13, 0.47, and 0.60 DA. Twenty-one of the 58 eyes had capillary nonperfusion before the IVB, and the mean (±SD) area of nonperfusion was 3.45 ± 4.66 DA before the IVB and 3.45 ± 5.19 DA 1 month after the IVB. This change was not significant (P = 0.36). An increase in the area of capillary nonperfusion of >1.0 DA after the IVB was seen in only 1 of all 58 eyes. CONCLUSION: : These results suggest that the incidence of a significant increase in the area of capillary nonperfusion (>1 DA) during the 1 month after the IVB is very low in eyes with branch retinal vein occlusion.

Correlation between focal macular electroretinograms and angiographic findings after photodynamic therapy.

PURPOSE: It is known that the amplitudes of the multifocal electroretinograms are generally reduced soon after photodynamic therapy (PDT). The purpose of this study was to determine whether this amplitude reduction correlates with the changes in macular thickness or with changes in choroidal circulation. METHODS: Thirty-seven eyes that were successfully treated by PDT were studied. Focal macular electroretinograms (fmERGs) and optical coherence tomography were performed before and 1 week, 1 month, and 3 months after PDT. Indocyanine green angiography was performed before and 3 months after PDT. The indocyanine green angiographic findings were classified into two groups: group A, with indistinct hypofluorescence at the site of the PDT, and group B, with well-defined hypofluorescence borders coinciding with the site of the PDT. RESULTS: The mean amplitudes of the fmERGs were significantly reduced at 1 week after PDT (P < 0.05). The correlations between the changes in the amplitude of the fmERG and the changes in macular thickness were not significant. Sixteen (43%) of the study eyes were classified into group A and 21 (57%) into group B by indocyanine green angiography. The mean ratio of the fmERG b-wave 1 week after PDT to that before PDT was 1.14 +/- 0.62 in group A and 0.65 +/- 0.29 in group B. This difference was statistically significant (P < 0.01). CONCLUSIONS: One of the possibilities that could explain the reduction in the amplitude of the fmERGs soon after PDT is the reduction in choroidal circulation caused by the PDT.

Better Visual Outcome by Intraocular Lens Ejection in Geriatric Patients with Ruptured Ocular Injuries.

Ocular trauma is one of the leading causes of visual impairment worldwide. Because of the popularity of cataract surgeries, aged individuals with ocular trauma commonly have a surgical wound in their eyes. The purpose of this study was to evaluate the visual outcome of cases that were coincident with intraocular lens (IOL) ejection in the eyes with ruptured open-globe ocular injuries. Consecutive patients with open-globe ocular injuries were first reviewed. Patients' characteristics, corrected distance visual acuities (CDVAs) over 3 years after the trauma, causes of injuries, traumatic wound patterns, and coexistence of retinal detachment were examined. The relationships between poor CDVA and the other factors, including the complications of crystalline lens and IOL ejection, were examined. A total of 105 eyes/patients [43 eyes with rupture, 33 with penetrating, 28 with intraocular foreign body (IOFB), and 1 with perforating injuries] were included. Rupture injuries were common in aged patients and were mostly caused by falls, whereas penetrating and IOFB injuries were common in young male patients. CDVAs of the eyes with rupture injuries were significantly worse than those of the eyes with penetrating or IOFB injuries. CDVA from more than 50% of the ruptured eyes resulted in no light perception or light perception to 20/500. CDVA of the ruptured eyes complicated by crystalline lens ejection was significantly worse than that of those complicated by IOL ejection. The wounds of the ruptured eyes complicated by IOL ejection were mainly located at the superior corneoscleral limbus, whereas those of the eyes complicated by crystalline lens ejection were located at the posterior sclera. There were significant correlations between poor CDVA and retinal detachment and crystalline lens ejection. These results proposed a new trend in the ocular injuries that commonly occur in aged patients; history of cataract surgery might affect the final visual outcome after open-globe ocular injuries.

Cross-sectional pupillographic evaluation of relative afferent pupillary defect in age-related macular degeneration.

To evaluate, using pupillography, the difference between eyes affected by age-related macular degeneration and their contralateral normal eyes with regard to the mean relative afferent pupillary defect (RAPD) score. Also, to ascertain any correlations between this difference in RAPD score and differences in visual acuity or age-related macular degeneration (AMD) dimensions. Measurements were made using the RAPDx pupillographer (Konan Medical, Nishinomiya, Japan), which analyzes pupil response to light stimulation. Both best corrected visual acuity (converted to logMAR) and greatest linear dimension (GLD; calculated on the basis of fluorescence angiography images) were measured. The correlations between RAPD difference and logMAR difference, and GLD difference were then analyzed. The study included 32 patients (18 men, 14 women; mean age = 74.8 ±â€Š9.7 years) who had AMD in 1 eye and a normal fundus in the contralateral eye. Mean resting pupil diameter, mean latency onset of constriction, mean velocity of constriction, and recovery were not significantly different in AMD eyes compared with normal eyes. The mean amplitude of constriction was smaller (P = 0.028), and the mean latency of maximum constriction was shorter (P = 0.0013) in AMD eyes than in normal eyes. Regarding RAPD scores, there was a significant correlation between visual acuity difference and RAPD score differences of both amplitude (P < 0.001, r = 0.53) and latency (P = 0.034, r = 0.33). GLD difference was also significantly correlated with differences in both amplitude (P = 0.021, r = 0.36) and latency (P = 0.033, r = 0.33) scores. RAPD outcomes were correlated with visual acuity and AMD dimension. Automated pupillography may be a useful tool in monitoring the progression of AMD and assessing changes in retinal function that result from novel interventions.

Development of a Fiber-Optic Optical Coherence Tomography Probe for Intraocular Use.

PURPOSE: To evaluate the performance of a newly developed 23-G optical coherence tomography (OCT) probe in animal and human eyes. METHODS: The probe is a side-imaging OCT device with a scanning beam set 43° to the optical axis and a working distance of 1.5 to 2.0 mm. The performance of the OCT probe was tested during vitrectomy in porcine cadaver eyes and rabbit eyes in situ. Optical coherence tomography images of a normal retina, retinal break, optic disc, pars plicata of the ciliary body, and intraoperative surgical manipulations were recorded. The probe was also tested in a pilot study of clinical cases; intraoperative real-time OCT imaging was performed in three patients, including a 56-year-old woman with an epiretinal membrane. RESULTS: The OCT probe was able to delineate intraocular tissues, including the posterior retina, and even the most peripheral pars plicata in animal eyes. The OCT probe also successfully delineated intraoperative surgical maneuvers such as membrane peeling and the minute structures of the vortex veins, ora serrata, and vitreous incarceration in the scleral incision from the trocar with sufficient resolution in the patients. There were no complications resulting from its use. CONCLUSIONS: The ability of this new 23-G OCT probe to obtain images of intraoperative manipulations from the most peripheral tissues in animal and patient eyes suggests that it could enable surgeons to make better decisions during the course of intraocular surgery.

Changes in retinochoroidal thickness after vitrectomy for proliferative diabetic retinopathy.

PURPOSE: To evaluate the changes in the peripheral retinochoroidal thickness after pars plana vitrectomy (PPV) with scatter photocoagulation for proliferative diabetic retinopathy (PDR). METHODS: Small gauge PPV was performed on 22 eyes with PDR with scatter photocoagulation, and on 32 eyes with an epiretinal membrane (ERM) without photocoagulation as control. The peripheral retinochoroidal thickness was measured at 5 mm from the limbus in the four quadrants using anterior segment optical coherence tomography preoperatively, and 3 days and 1 and 2 weeks after the surgery. In eyes with a peripheral choroidal detachment, the retinochoroidal thickness and the height of choroidal detachment were measured separately. The total peripheral thickness was defined as the sum of retinochoroidal thickness and the height of choroidal detachment. RESULTS: A significant larger number of eyes developed a choroidal detachment in the PDR group than in the ERM group 3 days after surgery (P < 0.001). The total peripheral choroidal thickness 3 days after surgery was significantly thicker than that before surgery in the PDR group (P = 0.009). The increase in the total peripheral thickness in the PDR group was significantly greater than that in the ERM group at 3 days after surgery (P = 0.007). The number of photocoagulation burns was significantly and positively correlated with the total peripheral thickness (r = 0.57, P = 0.006). CONCLUSIONS: We conclude that the transient thickening of the total peripheral thickness in early postoperative stage for PDR was due to the intraoperative scatter photocoagulation.

Correlation between macular volume and focal macular electroretinogram in patients with retinitis pigmentosa.

PURPOSE: To determine whether a significant correlation exists between the morphology of the macula measured by optical coherence tomography (OCT) and the amplitude of focal macular electroretinograms (fmERGs) in patients with retinitis pigmentosa (RP). METHODS: fmERGs were recorded in 43 patients with RP and 43 age-similar normal subjects, with a 15 degrees stimulus spot, 5.6 to 5.8 mm in diameter on the fundus. The sum of the volume of the neural retina in the central 6 mm (total macular volume) was measured with the OCT system. The length of the photoreceptor inner segment/outer segment junction (IS/OS line) in a 6-mm diameter macular area was also measured in the OCT images. RESULTS: There was a weak correlation between the total macular volume and the fmERG amplitudes (correlation coefficient, 0.46 for the a-wave and 0.54 for the b-wave). The fmERG amplitudes in the patients with RP with IS/OS line longer than 2 mm were significantly larger than those in patients with RP with IS/OS line shorter than 2 mm, but the correlations between these two factors were weak. One major reason for the low correlations between the macular morphology and fmERGs was that there were some patients with RP who had normal macular volume and long IS/OS line, but had severely reduced focal macular ERGs. CONCLUSIONS: Although the macular volume and length of the IS/OS line correlated weakly with the amplitude of the fmERGs, a preserved macular morphology does not necessarily guarantee normal-amplitude fmERGs in patients with RP.

Focal macular electroretinograms in eyes with wet-type age-related macular degeneration.

PURPOSE: To study the properties of the focal macular electroretinograms (fmERGs) in eyes with untreated wet-type age-related macular degeneration (AMD). METHODS: fmERGs were recorded from 157 eyes of 157 consecutive patients with untreated wet-type AMD (113 men, 44 women; age, 71.3 +/- 8.0 years). The fmERGs were recorded under direct fundus observation using a modified infrared fundus camera and a 15 degrees stimulus spot. Amplitudes and implicit times of the fmERGs recorded from the AMD patients were compared with those from 21 age-similar healthy controls. RESULTS: The amplitudes of fmERGs in the AMD patients were significantly smaller (P < 0.001) and the implicit times were significantly longer (P < 0.001) than the corresponding values in the control eyes. There was a significant correlation between amplitude and implicit time of the fmERG and visual acuity (logMAR), but the degree of correlation was weak. The difference in the b/a amplitude ratio between the AMD patients and healthy controls was not significant. CONCLUSIONS: The significant reduction in amplitude and the severe delay in implicit times of a- and b-waves of the fmERGs indicated significant functional alterations in the inner and the outer retinal layers of the macular area of eyes with wet-type AMD.