John O. Mason

Intravitreal concentration and clearance of triamcinolone acetonide in nonvitrectomized human eyes.

Purpose: To determine the intravitreal concentration and clearance of triamcinolone acetonide at various intervals after intravitreal injection into nonvitrectomized eyes. Methods: Six participants were administered 4 mg (0.1 cc) of triamcinolone acetonide ophthalmic suspension. All six eyes underwent therapeutic pars plana vitrectomy with membranectomy at various post injection intervals ranging from 1.25 to 5 months from the intravitreal injection. Undiluted specimens of vitreous overlying the macula and of aqueous humor were submitted for analysis. Vitreous and aqueous humor concentrations of triamcinolone were measured by high performance liquid chromatography. Results: Four eyes demonstrated detectable intravitreal concentrations of triamcinolone acetonide between 1.25 and 2.75 months after a single injection. Two eyes had an undetectable level of triamcinolone in both the vitreous and aqueous at 3 and 5 months post single injection. Conclusions: The intravitreal concentration of triamcinolone acetonide is detectable up to 2.75 months post a single 4 mg injection in nonvitrectomized eyes. A reinjection interval of 3 months may be needed to achieve sustained measurable levels of triamcinolone in nonvitrectomized patients.

Fibrocontractive Müller cell phenotypes in proliferative diabetic retinopathy.

PURPOSEnTo evaluate Müller cells as a potential source of fibrocontractive cells in proliferative diabetic retinopathy.nnnMETHODSnTemporal changes in glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, and alpha smooth muscle actin (alphaSMA) expression in cultures of freshly isolated porcine Müller cells were evaluated by indirect immunofluorescence and Western blotting. A similar evaluation was performed on freshly isolated Müller cells maintained in high- and low-glucose culture. Cryosections of six diabetic epiretinal tissues were evaluated for the same antigens.nnnRESULTSnMüller cell changes in culture included loss of glutamine synthetase and GFAP, with coincident gains in alphaSMA immunoreactivity. Vimentin immunoreactivity persisted without obvious change. Similar changes were observed when the cells were maintained in high- or low-glucose culture medium. All six diabetic epiretinal membranes contained positively identified Müller cells with vimentin, GFAP, and glutamine synthetase immunoreactivities. There was a progressive loss of glutamine synthetase and GFAP content and a coincident increase in alphaSMA content as the cells assumed an elongated, fibroblastlike morphology.nnnCONCLUSIONSnContinuous culture in high- versus low-glucose medium does not influence Müller cell phenotype changes. Positively identified Müller cells are present in diabetic epiretinal tissues and appear to undergo the same progression of phenotype changes observed in culture. Cells capable of generating tractional forces associated with proliferative diabetic retinopathy can arise from Müller cells.

Trans-luminal Nd: YAG laser embolysis for branch retinal artery occlusion

Purpose: To evaluate the clinical efficacy of transluminal YAG laser embolysis (TYE) for patients with severe vision loss secondary to a newly diagnosed branch retinal artery occlusion (BRAO) with visible emboli. Methods: Five eyes of five patients with acute, severe vision loss secondary to a branch retinal artery occlusion with visible emboli and retinal whitening were prospectively examined, enrolled, and underwent visual acuity testing, ophthalmic examination, color photography, and fluorescein angiography. Each patient was offered TYE and the potential risks of the treatment were explained. Follow-up examinations were undertaken postprocedure day 1 and subsequent follow-up depended on the clinical course. Results: In our five patients baseline best-corrected visual acuity (BCVA) was found to be 5/400, count fingers at 3 feet, count fingers at 5 feet, 20/800, and 20/200. All five of our patients showed improvement in BCVA 1 day after TYE. Fluorescein angiography showed immediate and dramatic restoration in flow past the obstructed arteriole in all patients. Patient 2 developed subretinal hemorrhage, which after vitrectomy and associated procedures the acuity improved to 20/25 at 22 days after the TYE. Final BCVA was 20/30, 20/25, 20/40, 20/30, and 20/40. Conclusion: TYE is a treatment modality to be considered in patients with BRAO who present acutely with severe vision loss and a visible embolus. The risks of TYE must be weighed against the possibility of severe and permanent loss of vision secondary to BRAO.

The Influence of Alloxan-Induced Diabetes on Müller Cell Contraction-Promoting Activities in Vitreous

PURPOSEnPrevious studies from this laboratory revealed that vitreous insulin-like growth factor biological activity increases in diabetes and that this change can precede the onset of proliferative diabetic retinopathy. The goal of this study was to characterize this phenomenon in an animal model of alloxan-induced diabetes.nnnMETHODSnSwine made diabetic with intravenous alloxan were euthanized at times varying from 0 to 90 days. Vitreous samples from normal and diabetic swine were evaluated for changes in Müller cell contraction-promoting activity, the presence of insulin-like growth factor binding protein (IGFBP), and carbonic anhydrase-I and -II. Ocular tissues from these animals were also evaluated for changes in contraction-promoting growth factors and IGFBP message levels.nnnRESULTSnAlloxan-induced diabetes is associated with significant increases in vitreous Müller cell contraction-promoting activity that are present in as few as 30 days and are sustained for at least 90 days. Biochemical studies revealed that the increases cannot be attributed to loss of growth factor-attenuating IGFBPs, changes in local expression of contraction-promoting growth factors, or vitreous hemorrhage.nnnCONCLUSIONSnThe previously reported increases in Müller cell contraction-promoting activity detected in human diabetic vitreous are present in diabetic swine within 30 days of chemical induction. The increase does not appear to be attributable to loss of growth factor control, increases in local growth factor expression, or vitreous hemorrhage, suggesting that other mechanisms are involved. It is the authors speculation that diabetes induces blood-vitreous barrier changes that allow a different subset of plasma proteins to enter vitreous fluids.

Nonsupine positioning is preferred by patients over face-down positioning and provides an equivalent closure rate in 25- and 23-gauge macular hole surgery.

PURPOSEnStrict face-down positioning after macular hole surgery is very difficult for most patients. Our study seeks to determine if alleviated positioning (avoidance of supine positioning) has equivalent successful closure rates when compared with face-down positioning. A patient survey was also performed to determine patient preference.nnnMETHODSnA single-center retrospective review of patients undergoing macular hole repair with a questionnaire completed by each patient after air bubble clearance summarizing the two postoperative scenarios. Patients were asked which positioning strategy they would choose if they were having repeat surgery. Eighty-two patients undergoing pars plana vitrectomy with primary full-thickness macular hole repair were identified. Repair was performed with either 3 days of strict face-down positioning (57 of 82 patients) or with the avoidance of supine positioning (25 of 82 patients) but no required face-down positioning.nnnRESULTSnThe anatomical success rates were similar between the 2 groups with 96% of final hole closure (55/57) in the face-down group versus 100% (25/25) in the nonsupine group. Macular hole size appeared to be similar between the 2 groups (a mean of 408 μm in face-down group vs. that of 483 μm in nonsupine group, with a median of 400 in both groups). Patient preference was in favor of less stringent nonsupine postoperative requirements. Although 100% (25/25) of the nonsupine group would opt for the same strategy with repeat surgery, only 51% (29/57) of the face-down group would opt for face-down positioning with repeat surgery (P < 0.001).nnnCONCLUSIONnThis study demonstrates equivalent closure rates among the patients who were assigned nonsupine versus face-down positioning postoperatively for macular hole repair, and that most patients would prefer to avoid strict face-down positioning if reoperated.

Acute multifocal hemorrhagic retinal vasculitis in a child: a case report

BackgroundAcute Multifocal Hemorrhagic Retinal Vasculitis (AMHRV) is a rare disease with unknown incidence that presents with abrupt onset of visual loss associated with retinal vasculitis, retinal hemorrhage, non-confluent posterior retinal infiltrates, vitreous cellular inflammation and papillitis in, otherwise, healthy adult individuals. The reported treatment options for Acute Multifocal Hemorrhagic Retinal Vasculitis are oral corticosteroids, intravitreal ganciclovir and laser photocoagulation or vitrectomy. We report a child with Acute Multifocal Hemorrhagic Retinal Vasculitis who was treated with aggressive immunosuppressive therapy resulting in a favorable visual outcome.Case presentationA retrospective case report of a 10-year-old African American girl who developed unilateral Acute Multifocal Hemorrhagic Retinal Vasculitis, which later on progressed bilaterally. We conducted a review of the clinical, laboratory and photographic records to evaluate her functional and anatomic outcome after aggressive immunosuppressive treatment. During the first 4xa0months of treatment of OD with intravitreal ganciclovir, intravitreal dexamethasone and systemic prednisone, the change in vision in OD improved from light perception (LP) to counting fingers (CF). During the next 18xa0months of aggressive systemic treatment of OD and the newly affected left eye (OS), the change in vision improved from CF in OD and CF in OS to 20/200 in OD and 20/80 in OS. Management during the 18-month interval included rituximab infusions, cyclophosphamide/methylprednisolone infusions, prednisone and mycophenolate.ConclusionsThis is the first reported case of Acute Multifocal Hemorrhagic Retinal Vasculitis occurring in a child. Ophthalmologists should be aware of the need to treat severe Acute Multifocal Hemorrhagic Retinal Vasculitis with aggressive immunosuppressive agents in collaboration with rheumatologists to obtain the best possible visual outcome.

Evaluation of proliferating cell abundance and phenotypes in proliferative diabetic retinopathy

BackgroundThe aim of this work is to evaluate the abundance, origins, and phenotypes of actively proliferating cells in proliferative diabetic retinopathy (PDR).MethodsEleven epiretinal membranes from patients undergoing surgery for PDR were evaluated by indirect immunofluorescence for evidence of cell proliferation using the nuclear cell proliferation marker Ki67 and for cell identities using glial fibrillary acidic protein (GFAP), glutamine synthetase, and α-smooth muscle actin (αSMA).ResultsKi67 positivity was consistently rare in PDR epiretinal membranes at 3.02u2009±u20091.42xa0% of the total cell population. The majority of the Ki67-positive cells were also positive for GFAP (74.0xa0%) with lower proportions positive for αSMA (30.7xa0%) and glutamine synthetase (1.5xa0%). Co-localization studies using glial and myoid markers revealed that virtually all (92xa0%) of the αSMA-positive cells are also GFAP positive and thus derive from glia.ConclusionsEntry into cell cycle and thus cell proliferation appears to be a rare phenomenon in PDR involving only a small percentage of the total cell population. Glia and/or glial-derived myofibroblasts appear to be the predominate cell types in epiretinal scar tissues and also account for the majority of the actively proliferating cells.