Short-term outcomes of intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and safety of loading phase treatment with 3 monthly intravitreal injections of faricimab for neovascular age-related macular degeneration (nAMD). METHODS: We retrospectively analyzed 16-week outcomes of 40 consecutive eyes of 38 patients with treatment-naïve nAMD. Three monthly injections of faricimab were administered to all eyes as a loading phase treatment. Best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), and dry macula achievement were all assessed every 4 weeks. Moreover, the regression of polypoidal lesions was evaluated after the loading phase. RESULTS: BCVA was 0.33 ± 0.41 at baseline and showed significant improvement to 0.22 ± 0.36 at week 16 (P < 0.01). Foveal thickness was 278 ± 116 µm at baseline, decreasing significantly to 173 ± 48 µm at week 16 (P < 0.01). CCT was 214 ± 98 µm at baseline, decreasing significantly to 192 ± 89 µm at week 16 (P < 0.01). Dry macula was achieved in 31 eyes (79.5%) at week 16. Indocyanine green angiography after the loading phase revealed complete regression of polypoidal lesions in 11 of 18 eyes (61.1%) with polypoidal lesions. One eye (2.5%) developed vitritis without visual loss at week 16. CONCLUSION: Loading phase treatment with intravitreal faricimab appears to generally be safe and effective for improving visual acuity and reducing exudative changes in eyes with nAMD.

Fungal Keratitis Caused by Talaromyces coalescens: A Case Report.

Fungal keratitis is a severe corneal infection, and the causative fungi include various rare fungal species. Fungal keratitis caused by Talaromyces species has yet to be reported, and there is no information about this fungus as a cause of keratitis. A 77-year-old man developed fungal keratitis while waiting for a donor cornea due to bullous keratopathy in his left eye. Fungal culture of a corneal scraping grew filamentous fungi, which were morphologically identified as Paecilomyces species. The corneal infection did not improve after topical administration of 1% voriconazole, and ribosomal DNA sequencing definitively verified the fungus to be Talaromyces coalescens. The lesion gradually improved after switching to topical 5% natamycin. Antifungal susceptibility tests determined the high minimum inhibitory concentrations of voriconazole to be > 8 µg/mL. This is the first report of Talaromyces fungal keratitis. Clinicians, especially those in ophthalmology, need to be aware of this rare fungus.

Chromatin reader Brd4 functions in Ig class switching as a repair complex adaptor of nonhomologous end-joining.

Class switch recombination (CSR) is a B cell-specific genomic alteration induced by activation-induced cytidine deaminase (AID)-dependent DNA break at the immunoglobulin heavy-chain locus, followed by repair. Although chromatin-associated factors in promoting AID-induced DNA break have been widely reported, the involvement of chromatin adaptors at the repair phase of CSR remains unknown. Here, we show that the acetylated histone reader Brd4 is critical for nonhomologous end-joining (NHEJ) repair of AID- and I-SceI-induced DNA breaks. Brd4 was recruited to the DNA break regions, and its depletion from the chromatin caused CSR impairment without affecting the DNA break generation. Inhibition of Brd4 suppressed the accumulation of 53BP1 and uracil DNA glycosylase at the switch regions, perturbed the switch junctional microhomology, and reduced Igh/c-myc translocation. We conclude that Brd4 serves as a chromatin platform required for the recruitment of repair components during CSR and general DNA damage.

Choroidal alterations during the clinical course of commotio retinae.

PURPOSE: To analyse the alterations in the choroidal structure of eyes with commotio retinae due to blunt-force trauma. METHODS: This retrospective study included 51 eyes of 50 patients who underwent swept-source optical coherence tomography (SS-OCT) during their initial visit and throughout their clinical course between March 2013 and February 2020. MAIN OUTCOMES AND MEASURES: This study focused on four choroidal measures: comparison of central choroidal thickness (CCT) between the injured and contralateral eyes immediately after injury, changes in the CCT, ratio of choroidal luminal and stromal properties in the injured eye during the clinical course and change in the suprachoroidal structure of the injured eye. RESULTS: In 44 eyes, the CCT was successfully compared between the injured and contralateral eyes. In 30 of these eyes (70%), the CCT in the injured eye was significantly thinner than that in the contralateral eye (P < 0.01). In 33 eyes, the clinical course of the injured eyes was followed. The CCT was increased and decreased by >30 µm in 11 (33%) and 6 eyes (18%), respectively, and remained the same in 16 eyes (49%). The ratio of luminal and stromal areas in the choroid had significantly increased from 1.72 ± 0.54 at the initial visit to 1.87 ± 0.55 at the last visit (P < 0.001). In four eyes, a hemispherical dark space was observed beneath the sclerochoroidal interphase at the initial visit. CONCLUSION: The choroidal structure and its luminal and stromal properties are dynamically altered during the clinical course of commotio retinae.

Comparison of the regressive effects of aflibercept and brolucizumab on pigment epithelial detachment.

BACKGROUND: To compare the regressive effects of aflibercept and brolucizumab on pigment epithelial detachment (PED) in age-related macular degeneration. METHODS: Eighty-three eyes of 83 patients diagnosed with type 1 macular neovascularization were included and retrospectively analysed using multimodal imaging. Forty-nine eyes were treated with intravitreal aflibercept injections (IVA group), and 34 eyes were treated with brolucizumab (IVBr group), with three consecutive injections administered as induction therapy. Before treatment and 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group. RESULTS: In the IVA group, MH at baseline (228 ± 169 µm) diminished to 180 ± 150 (P = 0.2558), 165 ± 140 (P = 0.0962), and 150 ± 129 µm (P = 0.0284) at 1, 2, and 3 months after treatment, respectively; the reduction at 3 months was significant. In contrast, in the IVBr group, the MH was 307 ± 254 µm before treatment, and it decreased to 183 ± 156 µm (P = 0.0113), 139 ± 114 µm (P = 0.0003), and 125 ± 126 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively, and the reduction at 1 month was significant. In both groups, the MD did not regress significantly. CONCLUSIONS: The results suggested that the MH of PED after IVBr treatment regressed faster than that after IVA treatment.

Intravitreal Aflibercept versus Brolucizumab for Treatment-Naive Neovascular Age-Related Macular Degeneration with Type 1 Macular Neovascularization: Comparison of Short-Term Outcomes.

INTRODUCTION: The purpose of this study was to evaluate the outcomes of loading-phase treatment with intravitreal aflibercept (IVA) or brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (nAMD) associated with type 1 macular neovascularization (MNV). METHODS: We retrospectively studied 108 consecutive eyes undergoing IVA and 103 consecutive eyes administered IVBr. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), dry macula achievement, polypoidal lesion regression, and development of intraocular inflammation (IOI) were all assessed. RESULTS: During the loading-phase treatment, IOI was detected in 18 eyes (17.5%) in the IVBr but none of those in the IVA group (p < 0.01). The loading-phase treatment was completed in 101 eyes in the IVA and 85 eyes in the IVBr group. In those cases, BCVA improved significantly, and CMT and CCT showed significant reductions after the loading-phase treatment in both groups (all p < 0.01). The CCT reduction was significantly greater with IVBr than with IVA (32 ± 28 µm vs. 40 ± 25 µm, p < 0.01). The dry macula achievement rate was significantly higher in the IVBr than in the IVA group (71.3 vs. 85.9%, p < 0.05). We observed complete regression of polypoidal lesions significantly more frequently with IVBr than with IVA (47.5 vs. 77.3%, p < 0.01). DISCUSSION/CONCLUSION: Loading-phase treatment with IVA or IVBr for treatment-naïve nAMD with type 1 MNV effectively improved BCVA and diminished exudative changes. The CCT reduction, dry macula achievement, and polypoidal lesion regression rates were all significantly greater in the IVBr than in the IVA group. The incidence of IOI was significantly higher with IVBr than with IVA.

Surgical outcomes of vitrectomy for intractable diabetic macular edema.

PURPOSE: To investigate clinical outcomes of vitrectomy for intractable diabetic macular edema (DME) in which anti-vascular endothelial growth factor (anti-VEGF) agents or periocular steroid were not effective. METHODS: This retrospective study examined 27 eyes of 25 cases. The main measurements included changes in visual acuity (VA) and retinal morphology. Vitrectomies were performed using the Constellation System 25G. RESULTS: Prior to undergoing vitrectomy, patients were treated with anti-VEGF agents or periocular injection of triamcinolone acetonide. The average number of anti-VEGF agent injections was 3.1 ± 2.8. Triamcinolone was used in 15 eyes. There was no significant change in the mean logMAR best-corrected visual acuity (BCVA) between baseline and posttreatment, with values of 0.49 ± 0.29 and 0.55 ± 0.33, respectively (P = 0.31). Compared with preoperative BCVA, postoperative BCVA improved by more than two lines in 4 eyes (14%), remained the same in 17 eyes (63%), and decreased in 6 eyes (23%). Morphologically, retinal thickness improved by more than 50 µm in 16 eyes (59%), remained unchanged in 7 eyes (26%), and increased in 5 eyes (18%). Retinal edema resolved in all of the cases in which macular epiretinal membrane (ERM) or vitreomacular traction (VMT) was detected by optical coherence tomography during pretreatment. CONCLUSIONS: Vitrectomy can potentially stabilize the retinal morphology in intractable DME and is likely more effective in DME cases accompanied by ERM or VMT.

Variation of vortex veins at the horizontal watershed in normal eyes.

PURPOSE: To assess the vascular pattern of choroidal vortex veins at the horizontal watershed zone in normal eyes using optical coherence tomography (OCT). METHODS: We retrospectively studied 207 normal eyes of 207 patients whose fellow eyes were diagnosed with unilateral retinal diseases without choroidal involvement. Venous anastomosis between the superior and inferior vortex veins and deviation of the horizontal watershed zone were evaluated using 12 × 12-mm en face OCT images. Central choroidal thickness (CCT) was measured on B-mode OCT images. RESULTS: Vortex vein anastomosis was observed in 92 eyes (44.4%) at the horizontal watershed zone. Superior or inferior deviation of the horizontal watershed was ascertained in 69 eyes (33.3%). The frequency of the anastomosis and deviation did not differ significantly between age groups (P = 0.56 and 0.96, respectively). Mean CCT of all eyes was 221 ± 80 µm. CCT was significantly greater in eyes with anastomosis than in those without (233 ± 73 µm vs 210 ± 83 µm, P < 0.05). However, CCT did not differ significantly between eyes with and without deviation of the horizontal watershed zone (223 ± 74 µm vs 219 ± 82 µm). CONCLUSIONS: Venous anastomosis at the horizontal watershed zone as well as superior or inferior deviation of the zone were frequently observed in normal eyes. CCT was greater in eyes with than in those without anastomosis, suggesting subclinical vortex vein congestion.

REDUCED VASCULAR DENSITY IN THE CHOROID AFTER TREATMENT WITH PHOTODYNAMIC THERAPY COMBINED WITH AFLIBERCEPT IN PATIENTS WITH POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate changes of vascular density in the choroid of patients with polypoidal choroidal vasculopathy treated with photodynamic therapy (PDT) combined with intravitreal aflibercept. METHODS: This study examined 12 eyes of 12 patients, who were diagnosed as polypoidal choroidal vasculopathy. All patents underwent optical coherence tomography before and at 3 months after PDT combined with intravitreal aflibercept treatment. Using en face optical coherence tomography images, we analyzed vascular density of the area outside the polypoidal choroidal vasculopathy lesion and within the PDT exposure area at the level of the choriocapillaris and middle layer of the choroid. In the outer layer of the choroid, the thickest vessel was selected in the area exposed to PDT, with the diameter of the vessel analyzed. RESULTS: The vascular density in the choriocapillaris and middle layer of the choroid significantly decreased from 0.54 ± 0.09 before treatment to 0.44 ± 0.07 after PDT treatment in the choriocapillaris and from 0.53 ± 0.10 to 0.47 ± 0.08 in the middle layer of the choroid, respectively. There was also a significant reduction in the diameter of the largest vessel from 309 ± 85 µm at baseline to 220 ± 52 µm. CONCLUSION: Photodynamic therapy may cause occlusion of the choriocapillaris and middle vessels in the choroid, as well as stenosis of the large vessels.

Retinal Detachment-Induced Müller Glial Cell Swelling Activates TRPV4 Ion Channels and Triggers Photoreceptor Death at Body Temperature.

Using region-specific injection of hyaluronic acid, we developed a mouse model of acute retinal detachment (RD) to investigate molecular mechanisms of photoreceptor cell death triggered by RD. We focused on the transient receptor potential vanilloid 4 (TRPV4) ion channel, which functions as a thermosensor, osmosensor, and/or mechanosensor. After RD, the number of apoptotic photoreceptors was reduced by ∼50% in TRPV4KO mice relative to wild-type mice, indicating the possible involvement of TRPV4 activation in RD-induced photoreceptor cell death. Furthermore, TRPV4 expressed in Müller glial cells can be activated by mechanical stimuli caused by RD-induced swelling of these cells, resulting in release of the cytokine MCP-1, which is reported as a mediator of Müller glia-derived strong mediator for RD-induced photoreceptor death. We also found that the TRPV4 activation by the Müller glial swelling was potentiated by body temperature. Together, our results suggest that RD adversely impacts photoreceptor viability via TRPV4-dependent cytokine release from Müller glial cells and that TRPV4 is part of a novel molecular pathway that could exacerbate the effects of hypoxia on photoreceptor survival after RD.SIGNIFICANCE STATEMENT Identification of the mechanisms of photoreceptor death in retinal detachment is required for establishment of therapeutic targets for preventing loss of visual acuity. In this study, we found that TRPV4 expressed in Müller glial cells can be activated by mechanical stimuli caused by RD-induced swelling of these cells, resulting in release of the cytokine MCP-1, which is reported as a mediator of Müller glia-derived strong mediator for RD-induced photoreceptor death. We also found that the TRPV4 activation by the Müller glial swelling was potentiated by body temperature. Hence, TRPV4 inhibition could suppress cell death in RD pathological conditions and suggests that TRPV4 in Müller glial cells might be a novel therapeutic target for preventing photoreceptor cell death after RD.

Clinical characteristics of pachydrusen in central serous chorioretinopathy.

PURPOSE: To evaluate the clinical characteristics of pachydrusen in central serous chorioretinopathy (CSC) and investigate the relationship between choroidal circulation and pachydrusen. METHODS: In a retrospective case series of 302 eyes of 151 patients with treatment-naïve CSC, we assessed the incidence of pachydrusen and their features on indocyanine green angiography (ICGA) and optical coherence tomography (OCT). RESULTS: Pachydrusen were observed in 82 of the 302 eyes (27.2%). The patients with pachydrusen were significantly older than those without pachydrusen. In 36 of the 82 eyes with pachydrusen, the choriocapillaris perfusion phase of ICGA was recorded. Pachydrusen were localized within the geographic filling delay of the choriocapillaris in 26 of the 36 eyes (72.2%). In the late phase of ICGA, pachydrusen corresponded to punctate hyperfluorescent spots in 69 of the 82 eyes (84.1%) and localized within sites of choroidal vascular hyperpermeability in 45 eyes (54.9%). En face OCT revealed pachydrusen to be localized over the dilated outer choroidal vessels in 70 of the 82 eyes (85.4%). B-mode OCT showed pachydrusen under the retinal pigment epithelium (RPE) in 72 of the 82 eyes (87.8%). There was no significant difference in central choroidal thickness between eyes with and without pachydrusen. CONCLUSIONS: Pachydrusen in patients with CSC were frequently localized within the choriocapillaris filling delay and over the dilated outer choroidal vessels. Moreover, they were frequently observed under the RPE and corresponded to punctate hyperfluorescent spots on ICGA. These findings suggest that inner choroidal circulation impairment due to dilatation of outer choroidal vessels might induce pachydrusen.

Isolates and antibiotic susceptibilities of endogenous bacterial endophthalmitis: A retrospective multicenter study in Japan.

Endogenous bacterial endophthalmitis, also called metastatic endophthalmitis, is a rare bacterial endophthalmitis derived from distant infectious foci via the bloodstream. This infection can potentially cause not only severe visual disturbance, but also loss of the eyeball or death, as most patients are immunocompromised. This retrospective Japanese multicenter study analyzed 32 eyes in 25 definitive cases. Twelve patients (48.0%) had diabetes mellitus. Typical ocular findings were vitreous haze (87.5%), cells in the anterior chambers (62.5%) and retinal infiltrates (50.0%). Elevated body temperature (64.0%), high serum C-reactive protein (96.0%) and leukocytosis (52.0%) were also frequently observed. Culture positivity rates for intraocular fluid were higher in the vitreous (62.5%) versus aqueous humor (28.6%). High positivity rates were also observed for blood (57.1%) and central venous catheters (100%). The most common pathogen was Staphylococcus aureus (10 cases), including methicillin-resistant S. aureus (4 cases). The next most common pathogen was Klebsiella pneumoniae (7 cases), which was highly associated with liver abscess. Compared to a previous 1991 national multicenter study, there has been a fourfold increase in the ratio of S. aureus. Antibiotic susceptibility tests revealed that all Gram-positives were susceptible to vancomycin and all Gram-negatives were susceptible to third-generation cephalosporins, imipenem/cilastatin, gentamycin and levofloxacin. Prognostic factors influencing poor visual outcome included poor initial visual acuity (p < 0.01), K. pneumoniae (p = 0.027) and gram-negative bacteria (p = 0.014) as the causative bacteria. Intravitreal antibiotic injection in combination with vancomycin and ceftazidime may be applicable for use as part of the standard treatment regimen for EBE.

Optical coherence tomography patterns and outcomes of contusion maculopathy caused by impact of sporting equipment.

BACKGROUND: To describe the patterns and outcomes of contusion maculopathy after ocular contusions resulting from accidental impact with sporting equipment. METHODS: We conducted a retrospective study of interventional case series. PATIENT POPULATION: Twenty-one eyes of 21 patients who sustained blunt ocular trauma while playing a sport. Intervention/Observation Procedure(s): Surgery or observation by optical coherence tomography (OCT). MAIN OUTCOME MEASURE(S): The morphologic changes within the macula in the early stages after injury and changes in visual function in the early and recovery stages after injury. RESULTS: In the early stage, OCT visualized four injury patterns: type Ι, commotio retinae (14.3%, 3 eyes) with increased reflectivity of the ellipsoid zone and retinal pigment epithelium; type II, incomplete macular hole(38.1%, 8 eyes) with three structural changes, i.e., a partial V-shaped macular hole, a jar-shaped macular hole with retinal tissue at the bottom, and a connective bridge attached to retinal tissues; type III, full-thickness macular hole (33.3%, 7 eyes); and type IV, foveal hemorrhage (14.3%, 3 eyes). During recovery, OCT images of types Ι and II showed almost normal macular morphology with better visual acuity (mean ± SD,0.02 ± 0.1 and 0.14 ± 0.21logMAR.). In types III and IV, the visual prognosis was poor (0.52 ± 0.34 and 0.22 ± 0.16), OCT images showed retinal atrophy at the fovea despite vitrectomy and sulfur hexafluoride (SF6) gas tamponade. CONCLUSION: Early OCT images identified four patterns of contusion maculopathy with different treatment outcomes. In types Ι and II, the visual function and retinal morphology remained intact. With types III and IV, respectively, the treatments of vitrectomy and SF6 gas tamponade for patients were effective.

Scedosporium apiospermum infectious scleritis following posterior subtenon triamcinolone acetonide injection: a case report and literature review.

BACKGROUND: Ubiquitous fungi of the Scedosporium apiospermum species complex (SASC) cause various opportunistic infections. Posterior subtenon triamcinolone acetonide (STTA) injection is a standard therapy for intraocular inflammation and macular edema. We report a case of Scedosporium apiospermum infectious scleritis after a posterior STTA injection. CASE PRESENTATION: A 75-year-old man received a posterior STTA injection to treat macular edema in his left eye. After 3 months, he complained of ocular pain and hyperemia in his left eye. Examination showed a subtenon abscess in the site corresponding with the STTA injection. After incising the abscess, the smear revealed numerous conidia-like structures. Although we suspected fungal infection and started topical voriconazole (VRCZ) and levofloxacin, the inflammation of the eye worsened. Fungal culture revealed filamentous fungus growth. Subsequently, we added systemic VRCZ and performed surgical debridement of the infected sclera and Tenon's capsule. Pathology of the sclera showed fungal hyphae. The antifungal susceptibility test revealed low minimum inhibitory concentrations for micafungin, VRCZ and miconazole (0.06, 0.25 and 0.5 µg/mL, respectively). After 2 months, the ciliary injection subsided and VRCZ therapy was stopped. However, subtenon abscess recurred 1 month after discontinuation of topical VRCZ. Surgical debridement and topical VRCZ were resumed, with the eye finally improving after 5 months of management. The fungal species was identified as Scedosporium apiospermum sensu stricto morphologically and by DNA sequencing. CONCLUSIONS: This case was successfully treated by topical and systemic VRCZ and repeated surgical debridement. Infectious scleritis caused by SASC rarely develops after posterior STTA. SASC can produce conidia in the enclosed subtenon space. Late-onset infectious scleritis after a posterior STTA injection suggests the presence of a fungal infection, including SASC, thereby requiring extensive and prolonged medical and surgical treatment.

Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

PURPOSE: To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. METHODS: We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. RESULTS: The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). CONCLUSIONS: Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended.

Genetic analysis of varicella-zoster virus in the aqueous humor in uveitis with severe hyphema.

BACKGROUND: Genetic variations have been identified in the genome of varicella-zoster virus (VZV) strains using vesicle fluid, varicella scabs and throat swab samples. We report a rare case of VZV-associated uveitis with severe hyphema, which was immediately diagnosed by polymerase chain reaction (PCR) using the aqueous humor, in which we were able to analyze the VZV genotype for the first time. CASE PRESENTATION: A 16-year-old Japanese boy was referred to our hospital with a 20-day history of unilateral anterior uveitis and 11-day history of hyphema. At presentation, details of the iris, the iridocorneal angle, and the fundus were not visible due to the severe hyphema. Serum anti-VZV IgG and anti-VZV IgM were elevated, and 1.61 × 109 copies/mL of VZV-DNA were detected by real-time PCR using the aqueous humor. As there were no eruptions on his face or body, we diagnosed zoster sine herpete and started intravenous administration of prednisolone and acyclovir. The hyphema completely disappeared 2 weeks after presentation, while sectorial iris atrophy and mild periphlebitis of the fundus became gradually apparent. Anterior inflammation and periphlebitis gradually improved and VZV-DNA in the aqueous humor was reduced to 1.02 × 106 copies/mL at 4 weeks after presentation. Examination by slit lamp microscope revealed no inflammation after 5 months, and VZV-DNA could no longer be detected in the aqueous humor. Serum anti-VZV IgG and anti-VZV IgM also showed a gradual decrease along with improvement in ocular inflammation. The genetic analysis of multiple open reading frames and the R5 variable repeat region in the VZV genes, using DNA extracted from the aqueous humor at presentation, showed that the isolate was a wild-type clade 2 VZV strain (prevalent in Japan and surrounding countries) with R5A allele and one SNP unique to clade 1 (both are major types in Europe and North America). CONCLUSIONS: VZV-associated uveitis may develop hyphema that obscures ocular inflammation, thus PCR analysis using the aqueous humor is the key investigation necessary for the diagnosis. The measurement of VZV-DNA copies by real-time PCR would be useful for evaluation of therapeutic effects. We could amplify and analyze VZV genotype using the aqueous humor including a very large number of VZV-DNA copies (1.61 × 109 copies/mL).

Two-year results of a treat-and-extend regimen with aflibercept for polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the effects of aflibercept therapy using a treat-and-extend regimen on treatment-naïve polypoidal choroidal vasculopathy (PCV). METHODS: In a retrospective interventional case series of 58 eyes of 58 patients with PCV, we assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and number of injections for 2 years. Polypoidal lesions were also evaluated before treatment and after the loading phase by indocyanine green angiography. RESULTS: BCVA significantly improved after the loading phase and was maintained in the maintenance phase. CMT and CCT significantly reduced after the loading phase and were maintained throughout the follow-up period. The number of injections averaged 7.72 in the first year and 4.67 in the second year. The average number of polypoidal lesions per patient was 2.43 before treatment. In 32 patients (55.2%), polypoidal lesions regressed completely after the loading phase; these patients also needed significantly fewer injections compared to other patients. CCT at baseline was positively correlated with the decreased amount of CCT after 2 years and negatively correlated with the number of injections for 2 years. CONCLUSIONS: Treat-and-extend intravitreal therapy with aflibercept may be effective for improving BCVA and exudative change in eyes with PCV. The regression of polypoidal lesions after the loading phase and thicker choroid at baseline might lead to fewer total number of intravitreal injections of aflibercept.

Two-Year Outcomes of a Treat-and-Extend Regimen Using Intravitreal Aflibercept Injections for Typical Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to evaluate the efficacy of a treat-and-extend (TAE) regimen using intravitreal injection of aflibercept (IVA) for typical age-related macular degeneration (tAMD). METHODS: We retrospectively studied 61 treatment-naïve eyes with tAMD. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of injections, and complications during 2 years were evaluated. RESULTS: BCVA significantly improved by on average 0.13 logMAR units, and CMT and CCT significantly decreased after 2 years. The number of injections was on average 13.6. In the second year, eyes with classic choroidal neovascularization (CNV) needed significantly fewer treatments than eyes with occult CNV. Fourteen eyes, which developed subfoveal fibrosis, showed significantly poorer BCVA after 2 years. Subfoveal fibrosis was significantly common in classic CNV. CONCLUSION: A TAE regimen using IVA for tAMD might be effective for improving BCVA and exudative changes. The exudation may be suppressed with fewer treatments in classic CNV compared to occult CNV.

The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells.

Just as normal stem cells require niche cells for survival, leukemia-initiating cells (LICs) may also require niche cells for their maintenance. Chronic myeloid leukemia (CML) is caused by the activity of BCR-ABL, a constitutively active tyrosine kinase. CML therapy with tyrosine kinase inhibitors is highly effective; however, due to the persistence of residual LICs, it is not curative. Several factors are known to support CML LICs, but purification of LICs and a thorough understanding of their niche signals have not yet been achieved. Using a CML-like mouse model of myeloproliferative disease, we demonstrate that CML LICs can be divided into CD25(+)FcεRIα(-) Lineage marker (Lin)(-) Sca-1(+)c-Kit(+) (F(-)LSK) cells and CD25(-)F(-)LSK cells. The CD25(+)F(-)LSK cells had multilineage differentiation capacity, with a preference toward cytokine-producing mast cell commitment. Although cells interconverted between CD25(-)F(-)LSK and CD25(+)F(-)LSK status, the CD25(+)F(-)LSK cells exhibited higher LIC capacity. Our findings suggest that interleukin-2 derived from the microenvironment and CD25 expressed on CML LICs constitute a novel signaling axis. The high levels of CD25 expression in the CD34(+)CD38(-) fraction of human CML cells indicate that CD25(+) LICs constitute an "LIC-derived niche" that could be preferentially targeted in therapy for CML.

Acute ganglion cell loss during rapid visual recovery in optic neuritis.

PURPOSE: To report dynamic changes in the retinal ganglion cell layer (GCL) and visual function in acute and chronic optic neuritis (ON). METHODS: Sixteen eyes (15 patients) with acute ON were followed for 3.5 to 31 months (average, 10.2). The best-corrected visual acuity (BCVA) and thickness of the GCL plus the inner plexiform layer (GCL+IPL) were measured 4 to 13 times between baseline and the final visit using the ganglion cell analysis software in the Cirrus HD-OCT [high-definition optical coherence tomography] instrument. Goldmann perimetry was performed at baseline and at the final visit. RESULTS: The thickness of the GCL+IPL at baseline was within normal limits in the affected (80.4 ± 4.9 microns) and unaffected fellow eyes (80.5 ± 5.0 microns). Rapid thinning to 69 ± 7.3 microns occurred during month 1 in the affected eyes, slowing during month 2, and then reaching a minimum level (63.6 ± 8.7 microns). In contrast, BCVA was lowest (mean ± standard deviation logarithm of the minimum angle of resolution, -1.29 ± 0.96) in 11 eyes at baseline, increased markedly to -0.15 ± 0.37 during month 1, and reached a maximum level (-0.18 ± 0.19) during month 2 and (-0.02 ± 0.23) at the final visit. The BCVA in the other five eyes fluctuated during month 1, increased markedly during month 2, and then reached a maximum plateau (-0.07 ± 0.20). The patterns of visual field defects at baseline were varied, and were determinants of BCVA. The visual field largely recovered in 11 eyes, but small central scotomas in four eyes and an enlarged blind spot in one eye remained at the final visit. Eyes with the least GCL+IPL thinning at month 1 or 2 had the least depression in the final deviation map. CONCLUSIONS: In acute ON, the progression toward irreversible ganglion cell loss occurs rapidly during months 1 and 2. In contrast, visual function recovers rapidly during the same period. Remodeling of the neural network may occur between the photoreceptors and the reduced numbers of ganglion cells during the first months of ON. The small number of residual ganglion cells appears to compensate for the initial visual dysfunction.