Ophthalmology

Purpose. Transgenic Col1a1 r/r mice develop elevated intraocular pressure (IOP) with an open angle and progressive optic nerve axon loss. The present study was undertaken to evaluate aqueous outflow facility and its age dependence in these mice. Methods. ...

Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn::GFP-positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn pe...

Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs). Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440) protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO). These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury.

Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn::GFP-positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn persisted in the same cells and increased with age. Accumulation of α-syn::GFP was reduced by immunization with single chain antibodies against α-syn. In conclusion, longitudinal live imaging of the retina in the PDGF-α-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of α-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting α-syn. Abnormal accumulation of α-synuclein (α-syn) is hypothesized to underlie the dopaminergic and non-dopaminergic neuronal cell death and synaptic dysfunction leading to motor and cognitive symptoms in Parkinson's disease (PD), PD dementia (PDD) and Dementia with Lewy Bodies (DLB) 1-4. Jointly, this heterogeneous group of disorders is referred to as Lewy body disease (LBD) 5. Although no model reproduces all disease relevant features, transgenic (tg) mouse models overexpressing α-syn have proved useful in characterizing specific behavioral, neuropathological, and biochemical consequences of α-syn aggregation (comprehensively overviewed 6). An ongoing effort in the field has been to find disease-relevant features in these transgenic mouse models with translational value for clinical trials in patients. Recent studies in the mThy1-α-syn transgenic (tg) (line 61) have revealed potentially clinically translatable alterations in bowel motility 7 , olfactory function 8 , hemodynamics 9 , and sleep disorders 10 , and these features parallel some the early and persistent symptoms in patients. In the search for translatable biomarkers, recent studies have investigated the patterns of α-syn accumulation in accessory structures of the CNS such as the eyes 11,12 and olfactory terminals 13 and in peripheral organs such as the gut 14,15 , skin 16 , heart 17 , and salivary glands 18. Among them, ophthalmologic alterations might be of interest because of its close proximity and connections between the eyes and the CNS. Varied degrees of changes in retinal structure and/or functional visual impairment have been observed in Parkinsonian patients and patients with other neurodegenerative diseases 19-25. Furthermore, recent studies have shown the presence of α-syn deposits in the retina in PD patients 11,12 .

Purpose: To evaluate the efficacy and safety of the fluocinolone acetonide (Retisert) implant compared with the dexamethasone (Ozurdex) implant in patients with noninfectious uveitis. Design: Comparative case series. Study Participants: Twenty-seven eyes received either the fluocinolone acetonide (FA) (n = 16) or dexamethasone (n = 11) implant. Methods: Chart review of patients at the Massachusetts Eye Research and Surgery Institution (MERSI) was done and patients were selected and matched according to age, sex, and type of uveitis. Eyes that received either the FA or dexamethasone implant, with follow-up ranging from 6 months to 2 years, were included. Main Outcome Measure: The recurrence rate of uveitis after implantation. Results: There were no significant differences in the baseline demographic characteristics. The majority of cases were idiopathic panuveitis, with 36.4% and 31.3% of eyes in the Ozurdex and Retisert groups, respectively. Recurrence rates of uveitis were 1.7 and 0.5 per 100 person-months in the Retisert and Ozurdex groups, respectively, with Retisert-implanted eyes 3.16 times more at risk of recurrence; however, this difference was not statistically significant (P = 0.41). No significant differences were seen in terms of improvement in inflammatory score and best-corrected visual acuity (BCVA). The median survival time for a second implant was 13 and 28 months for the Ozurdex and Retisert groups, respectively (P = 0.0028). Eyes with the Ozurdex were 5 times more likely to receive a second implant (P = 0.02). No eyes in the Ozurdex group needed additional glaucoma medications, surgery, or laser compared to 44% of eyes in the Retisert group. Eyes with the Retisert implant had a statistically higher rate of having more glaucoma medications, surgery, or laser (P = 0.02). In the Ozurdex group, 50% of phakic eyes at baseline had cataract progression and subsequent surgery compared with 100% of Retisert phakic eyes. Eyes with the Retisert implant are 4.7 times more at risk of cataract progression (P = 0.04). Conclusions: The dexamethasone (Ozurdex) implant seems comparable to the fluocinolone acetonide (Retisert) implant in preventing recurrence of noninfectious uveitis and in improving inflammation and BCVA. However, there were higher rates of cataract progression and need for glaucoma medications, laser, and surgery with the Retisert implant.

Purpose To evaluate the efficacy of bromfenac drops alone or with a single intravitreal injection of bevacizumab (IVB) or triamcinolone acetonide (IVTA) in the treatment of uveitic macular edema (UME). Design Comparative case series. Study Participant Sixty-seven eyes (of 55 patients) with UME that received either bromfenac drops alone (n=34), IVB plus bromfenac (n=21) or IVTA plus bromfenac (n=12). Methods Chart review of patients at the Massachusetts Eye Research and Surgery Institution (MERSI) was done. Eyes that received either bromfenac drops alone (Br), IVB plus bromfenac (IVB/Br) or IVTA plus bromfenac (IVTA/Br), with follow-up of up to 3 months, were included. Main Outcome Measure Visual acuity. Results There was no statistically significant effect seen in VA or CMT in the Br group, with 17 of 34 eyes (50 %) needing re-injection before 3 months of follow-up. Mean change in CMT at 4 weeks for the Br group was 5.06 µm. Compared to baseline, both the IVTA/Br and IVB/Br groups showed significant decrease in CMT and improvement in VA at 1 and 3 months follow-up. There was also a continuous decrease in CMT up to 3 months of follow-up with the IVTA/Br group, which was found to be significant in comparison with the IVB/Br group; this trend was not seen in the IVB/Br group at 3 months. The greatest mean change in CMT at 1 month was seen in the IVTA/Br group (154.33 ±178.22 µm), and this was statistically significant in comparison with the other groups (p=<0.0001). However, in terms of mean change in VA, there was no change in the Br group (0.01±0.11 VA logMAR), and only 0.12±0.19 and 0.15±0.20 in the IVB/Br and IVTA/Br groups, respectively. Conclusion IVB and IVTA are both effective in improving VA and decreasing CMT up to 3 months. Bromfenac is ineffective alone for UME treatment, but may have a synergistic effect with IVTA in reducing CMT up to 3 months of follow-up.

Well-differentiated papillary mesothelioma (WDPM) is an uncommon tumor that can be found in peritoneum, usually found as an incidentally small nodular lesion, without symptoms. It is considered an indolent neoplasia, however only a minority of patients presents survival longer than ten years. This report concerns a case of a 44 years-old woman, without history of asbestos exposure; with complaints of ascites, constipation, and a mass in cul-de-sac measuring 5,6 x 6,0 x 8,3cm. The tumor biopsy revealed morphology compatible with WDPM. Due to the impossibility of resection, she was treated with chemotherapy and presents 13 years of survival. Differential diagnosis with serous tumor of ovary was established through imunohistochemistry (CK7+, Calretinin+, CK20-, CEA- and CD15-) and ultrassonography. Considering size of tumor, impossibility of resection and symptomatology, this case has superior survival than described in literature.

OBJECTIVE:To describe urodynamic abnormalities in HTLV-1 infected individuals presenting urinary symptoms and verify if these findings and quality of life (QOL) evaluation correlate with overall neurological impairment. MATERIALS AND METHODS: From January/2001 to May/2004, 324 HTLV-1 seropositive subjects were evaluated to determine the occurrence of urinary symptoms. Urodynamic testing was performed in those who complained of frequency, urgency, or incontinence. They went through a complete clinical, neurological, and urological examination to investigate symptoms and signs of myelopathy. Neurological disability was assessed by Expanded Disability Status Scale (EDSS). RESULTS: From the 324 patients evaluated, 78 underwent the urodynamic testing. Fifty-seven individuals were females (73.1%) and age ranged from 23 to 76 years (mean = 48.7 years; SD ± 11.6). Urodynamic testing was abnormal in 63 patients (80.8%). The major abnormality was detrusor overactivity (DO), observed in 33 individuals (33/63; 52.4%), followed by detrusor-external sphincter dyssynergia (DESD), diagnosed in 15 subjects (15/63; 25.4%). HAM/TSP patients had significantly more DESD than the HTLV-I carriers (p = 0.005; OR = 5.5; CI: 1.6 to 19.4). QOL was severely compromised in HAM/TSP patients. CONCLUSIONS: Prominent urodynamic abnormalities were identified in individuals genuinely considered as HTLV-I carriers, suggesting an early compromise of the urinary tract; whereas HAM/TSP patients presented urodynamic findings, which posed a potential risk to the upper urinary tract (dyssynergia). Urodynamic evaluation should be performed in all HTLV-I-infected individuals with voiding complaints.

Objectives
To describe the frequency of urologic manifestations in human T-cell lymphotropic virus type I (HTLV-I) seropositive individuals from Salvador and other cities in Bahia, Brazil, with or without clinical HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Methods
A total of 218 HTLV-I seropositive subjects referred from blood banks or neurologic clinics were admitted to the HTLV-I multidisciplinary outpatient clinic from January 2001 to April 2004. They were assessed using a standardized questionnaire to determine urinary complaints and quality of life. Neurologic impairment was established using the Expanded Disability Status Scale (EDSS). HAM/TSP was considered as an EDSS score of 2 or greater.

Results
Nocturia (35.8%) was the most frequent finding, followed by incontinence (29.8%), urgency (25.2%), frequency (22.0%), and dysuria (15.6%). Differences were found between individuals with an EDSS score of 0 and those with an EDSS score greater than 0 but less than 2 regarding frequency, nocturia, urgency, urinary loss of any degree, and quality of life. Dysuria and great or total urinary loss were more frequent among those with severe HAM/TSP (EDSS score greater than 6).

Conclusions
Even HTLV-I subjects considered not to have HAM/TSP may have prominent urinary findings already present. Urologic manifestations, including nocturia and urinary loss, might be early manifestations of neurologic disease in those with HTLV-I.

Objective: To describe the efficacy of the propantheline bromide in neurogenic bladder in HTLV-I infected patients. Methods: From January/ 2001 to February/2004, twenty-one HTLV-I-carriers (7 men and 14 women) were selected for treatment with propantheline bromide 15 mg, PO, 2 to 3 times a day for 3 months, not discontinuing in the follow-up. At the end of the treatment period, patients were revaluated through specific questionnaires for urinary symptoms (UDI) and quality of life (Ditrovie). Results: From the 21 patients enrolled, 15 (71.4%) presented important clinical improvement, referring decrease of urinary frequency, urgency and loss, nocturia, and even total control of the dysfunction. Conclusion: We observed an efficient response to the anticholinergic agent propantheline bromide in urinary dysfunction caused by the HTLV-I.