Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.

Neuropathological changes associated with aberrant cerebrospinal fluid p-tau181 and Aß42 in Alzheimer's disease and other neurodegenerative diseases.

Recent studies suggest that increased cerebrospinal fluid (CSF) phospho-tau is associated with brain amyloid pathology rather than the tau pathology. However, confirmation using gold standard neuropathological assessments remains limited. This study aimed to determine background pathologies associated with aberrant CSF p-tau181 and amyloid-beta 1-42 (Aß42) in Alzheimer's disease (AD) and other neurodegenerative diseases. We retrospectively studied all patients with antemortem CSF and postmortem neuropathologic data at our institution. Comprehensive neuropathologic assessments were conducted for all patients, including Thal phase, Braak NFT stage, and CERAD score for AD. CSF concentrations of p-tau181 and Aß42 were compared between AD neuropathological scores at autopsy by one-way ANOVA stratified by other pathologies. A total of 127 patients with AD (n = 22), Lewy body disease (n = 26), primary tauopathies (n = 30), TDP-43 proteinopathy (n = 16), and other diseases (n = 33) were included. The age at lumbar puncture was 76.3 ± 9.1 years, 40.8% were female, and median time from lumbar puncture to autopsy was 637 (175-1625) days. While Braak NFT 0-II was prevalent without amyloid pathology, Braak NFT ≥IV was observed exclusively in patients with amyloid pathology. Stratified analyses showed that CSF p-tau181 was slightly but significantly higher in patients with high Thal phase or CERAD score even in those with Braak NFT 0-II at autopsy. In patients with amyloid pathology, CSF p-tau181 was significantly and more profoundly elevated in those with Braak NFT ≥III at autopsy. CSF Aß42 was lower in patients with high amyloid pathological scores. However, 34% with Thal ≤ 2 and 38% with CERAD ≤ sparse also showed decreased Aß42. Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) were overrepresented in this group. These results neuropathologically confirmed previous studies that CSF p-tau181 levels were slightly elevated with amyloid pathology alone and were even higher with tau pathology, and that CSFAß42 can be decreased in PSP/CBD.

CSF P-Tau181 and Other Biomarkers in Patients With Neuronal Intranuclear Inclusion Disease.

BACKGROUND AND OBJECTIVES: CSF tau phosphorylated at threonine 181 (p-tau181) is a widely used biomarker for Alzheimer disease (AD) and has recently been regarded to reflect ß-amyloid and/or p-tau deposition in the AD brain. Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by intranuclear inclusions in neurons, glial cells, and other somatic cells. Symptoms include dementia, neuropathy, and others. CSF biomarkers were not reported. The objective of this study was to investigate whether CSF biomarkers including p-tau181 are altered in patients with NIID. METHODS: This was a retrospective observational study. CSF concentrations of p-tau181, total tau, amyloid-beta 1-42 (Aß42), monoamine metabolites homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) were compared between 12 patients with NIID, 120 patients with Alzheimer clinical syndrome biologically confirmed based on CSF biomarker profiles, and patients clinically diagnosed with other neurocognitive disorders (dementia with Lewy bodies [DLB], 24; frontotemporal dementia [FTD], 13; progressive supranuclear palsy [PSP], 21; and corticobasal syndrome [CBS], 13). Amyloid PET using Pittsburgh compound B (PiB) was performed in 6 patients with NIID. RESULTS: The mean age of patients with NIID, AD, DLB, FTD, PSP, and CBS was 71.3, 74.6, 76.8, 70.2, 75.5, and 71.9 years, respectively. CSF p-tau181 was significantly higher in NIID (72.7 ± 24.8 pg/mL) compared with DLB, PSP, and CBS and was comparable between NIID and AD. CSF p-tau181 was above the cutoff value (50.0 pg/mL) in 11 of 12 patients with NIID (91.7%). Within these patients, only 2 patients showed decreased CSF Aß42, and these patients showed negative or mild local accumulation in PiB PET, respectively. PiB PET scans were negative in the remaining 4 patients tested. The proportion of patients with increased CSF p-tau181 and normal Aß42 (A-T+) was significantly higher in NIID (75%) compared with DLB, PSP, and CBS (4.2%, 4.8%, and 7.7%, respectively). CSF HVA and 5-HIAA concentrations were significantly higher in patients with NIID compared with disease controls. DISCUSSION: CSF p-tau181 was increased in patients with NIID without amyloid accumulation. Although the deposition of p-tau has not been reported in NIID brains, the molecular mechanism of tau phosphorylation or secretion of p-tau may be altered in NIID.

Aseptic Meningitis-retention Syndrome Associated with Tocilizumab in a Patient with Idiopathic Multicentric Castleman Disease.

This is the first report of tocilizumab-associated meningitis-retention syndrome in a patient with idiopathic multicentric Castleman disease. A 57-year-old man presented with headache, nuchal rigidity, impaired consciousness, pyramidal tract signs and urinary retention. A cerebrospinal fluid examination revealed increased cell counts and protein levels. These symptoms were improved by intravenous methylprednisolone. Tocilizumab-associated meningoencephalitis has been reported in patients with rheumatoid arthritis and juvenile idiopathic arthritis but not with multicentric Castleman disease. This case presents evidence of the increased probability of meningitis as a neurological complication of tocilizumab administration.

A central nervous system metastasis of melanoma with stroke-like onset of left-lower quadrantanopsia.

"Stroke mimics" mean diseases presenting with acute neurological impairments that are taken for stroke. Discriminating them is crucial to avoid improper treatment or delayed correct treatment. We describe a 48-year-old woman presenting with a sudden onset of scintillating scotoma and left-lower quadrantanopsia. Hyperacute cerebral infarction was suspected. However, brain magnetic resonance imaging (MRI) revealed a mass at the cortico-medullary junction in the right occipital lobe. We diagnosed her as metastatic melanoma. We suspected that neurological deficits can be attributed to seizure, and therefore introduced levetiracetam. She showed neurological improvement immediately. Our case demonstrated the importance of considering brain tumor as a differential diagnosis in patients presenting with acute-onset neurological deficits. In addition to appropriate treatment of tumor, the use of newer antiepileptic drugs resulted in good neurological prognosis in metastatic brain tumors.

Corticobasal degeneration with deep white matter lesion diagnosed by brain biopsy.

Corticobasal degeneration (CBD) is a rare progressive neurodegenerative disorder characterized by asymmetric presentation of cerebral cortex signs, cortical sensory disturbance and extrapyramidal signs. Herein, we report a case of a 66-year-old Japanese woman who presented with apraxia of the right hand. She subsequently developed postural instability and cognitive impairments that rapidly worsened. One and a half years later, the patient was wheelchair-bound and severely demented. Brain magnetic resonance imaging revealed left dominant atrophy of the frontoparietal lobe. There was a hyperintense lesion in the deep white matter expanding toward the subcortical area on fluid-attenuated inversion recovery (FLAIR) images. In order to rule out the possibility of an intracranial tumor such as an astrocytoma or malignant lymphoma, we performed a brain biopsy of the left frontal middle gyrus. The patient became bedridden and showed akinetic mutism 1 year after biopsy. Pathological examination revealed a large amount of 4-repeat tau-immunoreactive neuropil threads scattered predominantly in the corticomedullary junction and tau-immunoreactive structures, consistent with CBD. Immunostaining for p53 showed no positive cells, and there were very few Ki-67-positive cells. On immunoblots of sarkosyl-insoluble brain extracts, a major doublet of 64 and 68 kDa full-length tau with two closely related fragments of approximately 37 kDa were detected. Based on these results, the patient was pathologically diagnosed as having CBD, excluding the possibility of tumor. Taken together with previous similar case reports, our findings indicate that a deep white matter hyperintense lesion on FLAIR images may be a useful clue to CBD, predicting rapid clinical progression with severe dementia based on severe white matter degeneration with a large amount of tau accumulation on pathological examination.

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß2-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß2-microglobulin level higher than 10,000 µg/g cr. and a blood cadmium level higher than 6 µg/L or urinary cadmium level higher than 10 µg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).

Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration.

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.

Efficacy of intravitreal aflibercept injections for Japanese patients with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the efficacy of intravitreal aflibercept therapy in treatment-naïve Japanese patients with polypoidal choroidal vasculopathy (PCV) using Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. SUBJECTS AND METHODS: This study was a prospective, nonrandomized, interventional exploratory clinical trial performed in an institutional setting. Patients with PCV were treated with intravitreal aflibercept 2 mg/0.05 mL every 2 months after 3 initial monthly doses, for 1 year. Visual acuity test using the ETDRS chart and indocyanine green angiography was performed at baseline and at 6 and 12 months after initiating the treatment, in addition to routine examinations performed at each visit. The main outcome measure was the proportion of patients who achieved <15 ETDRS letter score loss. RESULTS: Twenty-two patients were enrolled in this study. Nineteen (86%) patients were eligible for analysis. All the patients maintained their visual acuity (<15 ETDRS letter score loss) at 12 months. The ETDRS letter scores were 64.1 at baseline and 69.8 at 12 months (P<0.039). The polyps regressed completely in 14 (74%) patients at 12 months. Cataract progressed in 1 eye, but this progression was considered to be a senile change. CONCLUSIONS: Japanese patients with treatment-naïve PCV, who were treated with intravitreal aflibercept every 2 months after 3 initial monthly doses, exhibited a significant increase in ETDRS letter scores and a high rate of polyp resolution at 12 months.

Clinical features of a toddler with bilateral bullous retinoschisis with a novel RS1 mutation.

PURPOSE: To report the clinical and genetic findings of a male toddler who presented bilateral bullous retinoschisis with a novel RS1 mutation. OBSERVATIONS: This is an observational case report of a patient referred to our hospital with esotropia. A comprehensive ophthalmic examination was performed with the boy (age, 1 year 4 months) under general anesthesia that included fundus examinations, fluorescein angiography (FA), swept-source optical coherence tomography (SS-OCT), and full-field electroretinography (FF-ERG). Genetic analysis of the coding region in the RS1 gene was performed by Sanger sequencing for the patient and mother. There was a family history of X-linked retinoschisis (XLRS). Fundus examinations and FA showed bullous retinoschisis bilaterally in the inferior retina. The SS-OCT images showed two kinds of schisis in the inner nuclear layer (INL) and more proximally. In general, the inner plexiform layer, ganglion cell layer, and retinal nerve fiber layer are in the proximal INL; however, in this case there was hyperreflective tissue with a rough surface instead of normal retinal layers. In addition, in the schisis cavity between the hyperreflective tissue and separated retina, a number of hyperreflective fiber-like strands arose from the hyperreflective tissue and extended to the schisis cavity. During the follow-up period, the bullous retinoschisis collapsed spontaneously in the right eye. FF-ERG showed a reduced b-wave and relatively preserved a-wave in all components. Genetic analysis showed a novel RS1 mutation (c.185_186insT, p.E62DfsX24 in exon 4) in the patient and mother. CONCLUSIONS AND IMPORTANCE: We report the detailed retinal structure in a genetically identified case of bullous retinoschisis. The notable finding was that the cavity of bullous retinoschisis contained a number of fiber-like strands as observed in the cavity of typical retinoschisis.

Comparison of Time to Retreatment and Visual Function Between Ranibizumab and Aflibercept in Age-Related Macular Degeneration.

PURPOSE: To compare time to retreatment and visual function between patients with treatment-naïve neovascular age-related macular degeneration (AMD) treated with either intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA) in routine clinical practice. DESIGN: Retrospective, interventional comparative case series. PARTICIPANTS: A total of 200 eyes of 197 patients with neovascular AMD. METHODS: A total of 99 patients in the IVR group and 101 patients in the IVA group who met the inclusion criteria with 12 months of follow-up were included in the present study. All patients received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab or 2.0 mg/0.05 mL aflibercept as loading doses. Retreatment was allowed if evidence of clinical deterioration or the presence of intraretinal edema or subretinal fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The time to retreatment after the third injection during the loading phase to the first recurrence during the maintenance phase was compared between treatments using the Kaplan-Meier analysis. Functional and anatomic outcomes were also compared between the IVR and IVA groups. RESULTS: The median time to retreatment after the last induction dose was 5 months in both groups. The proportion of IVR patients who required injection retreatment was not significantly higher than that of IVA patients (67.7% and 63.4%, respectively, at the 12-month follow up; log-rank test, P = .554). In both groups, significant improvements in postoperative best-corrected visual acuity (BCVA) compared with preoperative visual acuity was observed over the 12-month follow-up period (P < .05 for both). Central foveal thickness (CFT) decreased from the baseline values in both groups during the follow-up period (P < .001 for both). Although there was a trend toward greater BCVA improvements in the IVA group, no significant differences in BCVA or CFT were observed between the treatment groups. CONCLUSIONS: Both IVR and IVA were well tolerated and demonstrated efficacy in improving the visual acuity in treatment-naïve patients with AMD. Despite a trend toward greater BCVA improvements in the IVA group, a similar injection burden was observed following the loading phases of both ranibizumab and aflibercept.

AFLIBERCEPT FOR POLYPOIDAL CHOROIDAL VASCULOPATHY: As Needed Versus Fixed Interval Dosing.

PURPOSE: To evaluate the functional and morphologic outcomes of patients with polypoidal choroidal vasculopathy undergoing intravitreal aflibercept (IVA) treatment using every 2-month injections compared with a pro re nata (PRN) regimen after 3 initial monthly doses. METHODS: The authors prospectively studied all the treatment-naive patients with polypoidal choroidal vasculopathy who were scheduled to undergo IVA using every 2-month injections or PRN after induction treatment between March 2013 and October 2013. All patients who had a follow-up period of 1 year or longer were included in the study. The best-corrected visual acuity in the 2 groups was compared before treatment and at 4 months, 6 months, and 12 months after the initial treatment. The regression of the polyps was also assessed using indocyanine-green angiography at baseline and 12 months. RESULTS: Forty-two eyes were assessed at the 12-month follow-up examination. Twenty-five eyes were treated with IVA injections every 2-month after 3 initial monthly doses, and 17 eyes were treated using PRN after loading doses. The mean number of administered IVA was 7.0 in the every 2-month group and 5.0 ± 2.9 in the PRN group, with significant difference between the 2 groups (P < 0.01). Both groups showed significant improvement of the mean logarithm of the minimum angle of resolution values for best-corrected visual acuity at 12 months, as compared with baseline values (P < 0.01 in every 8-week group and P = 0.03 in PRN group, respectively). No significant difference in the improvement of best-corrected visual acuity between the 2 groups was observed at baseline or at 4 months, 6 months, and 12 months after treatment (P > 0.05, respectively) although there was a trend toward better results in the every 8-week group. The rate of polyp regression was 48.0% (12/25) in the every 8-week group and 52.9% (9/17) in the PRN group, with no significant difference between the 2 groups (P = 0.50). CONCLUSION: Among the 2 treatment modalities, IVA was well tolerated and improved the visual outcomes in patients with polypoidal choroidal vasculopathy as evaluated at 1-year follow-up examinations. However, there was a trend toward better vision improvement with fixed treatment every 2 months.

Long-term Outcomes After Preoperative Intravitreal Injection of Bevacizumab Before Trabeculectomy for Neovascular Glaucoma.

PURPOSE: To evaluate the long-term (>3 y) outcomes of patients given preoperative intravitreal bevacizumab (IVB) injection before trabeculectomy for neovascular glaucoma (NVG). METHOD: We performed a retrospective study of a consecutive series of 12 eyes of 11 patients who underwent trabeculectomy with mitomycin C combined with preoperative IVB for NVG at our institution between April 2009 and April 2010. The mean follow-up period was 43.0±7.0 months (range, 36 to 51 mo), and all patients were followed up for at least 36 months. Surgical success was defined as an intraocular pressure (IOP) of ≤21 mm Hg with or without topical ocular hypotensive medication. RESULT: The cumulative surgical success rate was 83.3% at 1 year and 83.3% at 3 years. The mean IOP before surgery was 42.7±9.2 mm Hg, whereas the mean postoperative IOP was significantly lower, being 15.1±3.7 mm Hg at 1 year and 14.2±3.2 mm Hg at 3 years (P<0.01).In contrast, no significant change of the mean visual acuity as compared with the preoperative visual acuity was observed at the follow-up carried out 3 years after the surgery. Intraoperative and early postoperative hyphema was seen in 2 eyes. Recurrence of neovascularization requiring additional IVB injection was seen in 3 eyes. CONCLUSIONS: Preoperative IVB injection before trabeculectomy for NVG might be effective over the long-term (>3 y) control of the IOP.

Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the results of a 3-year follow-up of intravitreal pegaptanib sodium injection as maintenance therapy for the treatment of neovascular age-related macular degeneration (AMD) in Japanese patients. METHODS: In this prospective, uncontrolled interventional study, 20 eyes of 19 patients with treatment-naïve AMD who had received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as the induction treatment and had shown clinical/anatomical improvement were enrolled. An intravitreal injection of 0.3 mg/0.09 mL pegaptanib sodium was administered as the maintenance therapy every 6 weeks. Booster treatments using ranibizumab were allowed if clinical deterioration was judged to be present. The primary outcome measures were the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) as evaluated using spectral-domain optical coherence tomography. RESULTS: Sixteen of the 20 eyes (80 %) were assessed at the 3-year follow-up. The mean logMAR BCVA improved significantly from 0.56 ± 0.31 before the induction treatment to 0.24 ± 0.25 at baseline (P < 0.001) and was well maintained at 156 weeks (0.25 ± 0.28, P = 0.938). Moreover, the mean CFT also decreased significantly from 346 ± 111 µm before the induction treatment to 232 ± 54 µm at baseline (P < 0.001) and was well preserved at 156 weeks (210 ± 59 µm, P = 0.278). Thirteen eyes (81.3 %) received an unscheduled booster treatment, and no severe systemic or ocular side effects occurred during follow-up. CONCLUSION: Intravitreal pegaptanib sodium injection as the maintenance therapy was effective in stabilizing the vision of patients with AMD in whom induction treatment led to improved BCVA, as evaluated at the 3-year follow-up.

Outcomes of microincision vitrectomy surgery with internal limiting membrane peeling for macular edema secondary to branch retinal vein occlusion.

PURPOSE: To evaluate the anatomic and functional effect of microincision vitrectomy surgery (MIVS) with internal limiting membrane (ILM) peeling for macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: The medical records of 101 eyes of 101 patients who had undergone MIVS with ILM peeling for macular edema secondary to BRVO were studied. Patients were classified into ischemic and non-ischemic BRVO based on angiograph. The best-corrected visual acuity (BCVA) and central foveal thickness (CFT), determined by spectral domain optical coherence tomography, were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: Preoperative mean logarithm of the minimum angle of resolution (logMAR) BCVA ± standard deviation (SD) was 0.52±0.43 and mean CFT ± SD was 489.4±224.9 µm. Postoperative mean BCVA ± SD values were 0.41±0.35, 0.35±0.41, 0.29±0.36, and 0.25±0.41, and mean CFT values were 370.1±148.9, 327.5±157.5, 310.9±154.9, and 274.4±135.3 µm at 1, 3, 6, 12 months, respectively. The mean BCVA was significantly improved at 3, 6, and 12 months postoperatively (all P<0.05), and the mean CFT was significantly decreased at all postoperative follow-up time points (all P<0.05). At the 12-month postoperative evaluation, BCVA had improved by 0.2 logMAR units in 50 eyes (60.0%) with ischemic BRVO and in nine eyes (50.0%) with non-ischemic BRVO. Six eyes (6.0%) experienced recurrence or persistence of macular edema at 12 months postoperatively. CONCLUSION: MIVS with ILM peeling for macular edema secondary to BRVO is effective in improving visual acuity and foveal morphology with low recurrence of macular edema.

Displacement of submacular hemorrhages in age-related macular degeneration with subretinal tissue plasminogen activator and air.

OBJECTIVE: To study the anatomic and visual outcomes of a surgical procedure in which tissue plasminogen activator and air are injected subretinally to displace massive submacular hemorrhages secondary to age-related macular degeneration. DESIGN: Prospective, consecutive, interventional case series. PARTICIPANTS: Thirteen consecutive patients (13 eyes) with massive submacular hemorrhages secondary to age-related macular degeneration. INTERVENTION: The surgical procedure consisted of a 25-gauge vitrectomy and submacular injection of tissue plasminogen activator (25 µg) and 0.4 ml air with a microneedle having an outer diameter of 50 µm. The procedure was followed by having the patient remain in the prone position overnight. MAIN OUTCOME MEASURES: Mean visual acuity change from baseline, mean central lesion thickness change from baseline, fluorescein angiography findings, and surgical complications. RESULTS: Total subfoveal blood displacement was achieved in all 13 eyes (100%). Central lesion thickness decreased from a mean baseline value of 867 µm to a mean value of 379 µm at 1 month after surgery. There was visual improvement in 11 eyes, no visual improvement in 1 eye, and poorer vision in 1 eye. The mean change in Early Treatment Diabetic Retinopathy Study letter score from baseline was 19.4 letters at 1 month (P = 0.006) and 23.3 letters at 3 months (P = 0.001). There was intraoperative macular hole formation. CONCLUSIONS: Submacular air injection with a microneedle facilitates displacement of clots dissolved with tissue plasminogen activator with few complications and results in earlier visual improvement.

Intravitreal injection of ranibizumab using a pro re nata regimen for age-related macular degeneration and vision-related quality of life.

BACKGROUND: The purpose of this study was to assess visual function and vision-related quality of life after intravitreal injection of ranibizumab (IVR) using a pro re nata regimen for the treatment of age-related macular degeneration. METHODS: A prospective study of 54 eyes in 54 patients scheduled to undergo IVR for the treatment of exudative age-related macular degeneration was performed. A self-administered, 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was completed before and 3 and 12 months after the initial IVR treatment. We evaluated logMAR visual acuity and NEI VFQ-25 scores preoperatively and postoperatively. Further, associations between the changes in NEI VFQ-25 scores and patient characteristics were investigated at 12 months. RESULTS: Postoperative best-corrected visual acuity improved significantly when compared with the preoperative visual acuity throughout the 12-month period (P<0.05 at 3 and 12 months, respectively). On the other hand, IVR treatment significantly improved the postoperative NEI VFQ-25 mean composite score at both 3 and 12 months (P<0.05, respectively). Better visual acuity at 12 months was associated with a greater improvement in NEI VFQ-25 score at 12 months (P<0.05). CONCLUSION: IVR was well tolerated and improved vision in these patients with age-related macular degeneration, as evaluated at one-year follow-up examinations. IVR also enabled good subjective perception, as indicated by higher composite NEI VFQ-25 scores. Maintaining good visual acuity may be an important factor for improving vision-related quality of life.