Surgical outcomes of 25-gauge pars plana vitrectomy for diabetic tractional retinal detachment.

PURPOSE: To evaluate the outcomes and complications of 25-gauge (G) pars plana vitrectomy (PPV) for repair of diabetic tractional retinal detachment (TRD). METHODS: Retrospective review of consecutive, single-surgeon 25-G PPV cases between July 2007 and July 2014. Seventy eyes from 55 patients were operated on for diabetic TRD; all eyes were tamponaded with sulfur hexafluoride, octofluoropropane, silicone oil, or balanced salt solution. Mean age at surgery was 47.7 years (range 23-76 years), and mean length of follow-up was 713 days (range 90-2368 days; median 671 days). Primary outcomes included best-corrected visual acuity (BCVA), intraocular pressure (IOP), anatomic success, redetachment, and endophthalmitis. RESULTS: Preoperatively, 49 eyes (70%) had a concurrent rhegmatogenous component (8 of which also had proliferative vitreoretinopathy (PVR)). Mean BCVA improved from logarithm of the minimal angle of resolution 1.59 (20/800, SD 0.88) to 0.68 postoperatively (20/100, 0.77), P-value<0.001. Mean IOP increased from 15.9 to 20 mm Hg 1 day after surgery. Elevated postoperative IOP (≥ 22 mm Hg) occurred in 25 eyes, and low IOP (≤ 5 mm Hg) occurred in 2 eyes. Primary reattachment was achieved in 63 eyes (90%), and final anatomical success occurred in 69 eyes (99%). There were no cases of endophthalmitis. CONCLUSIONS: Twenty-five-G PPV repair was safe and effective in the repair of diabetic TRD, including eyes with a combined rhegmatogenous detachment or PVR. Gas, silicone oil, and balanced salt solution tamponading agents all proved to be efficacious in this surgical population.

Rapid response of retinal pigment epithelial detachments to intravitreal aflibercept in neovascular age-related macular degeneration refractory to bevacizumab and ranibizumab.

PURPOSE: The aim of this study is to report the short-term efficacy of aflibercept in the treatment of neovascular age-related macular degeneration (AMD) with associated retinal pigment epithelial detachment (PED) which is refractory or develops tachyphylaxis to bevacizumab and ranibizumab. METHODS: The method comprised a retrospective review of the medical records of patients with neovascular AMD and associated PEDs recently treated with aflibercept and previously treated with bevacizumab and ranibizumab. RESULTS: Three eyes of three female patients of ages 49, 55, and 65 years old with large serous PEDs and subretinal fluid (SRF) associated with occult choroidal neovascularization and neovascular AMD were treated with aflibercept after intravitreal bevacizumab and/or ranibizumab failed to resolve the lesions. All had complete resolution of SRF and complete or near-complete resolution of the PEDs after aflibercept injections over a 3-month period. Visual acuity improved in all three eyes. CONCLUSION: Intravitreal aflibercept may be an effective treatment option for serous PED in neovascular AMD patients after bevacizumab and ranibizumab have previously failed. Larger studies with longer follow-up are required to determine the role of aflibercept in treatment of PED in neovascular AMD.

Compressive mechanical properties of bovine cortical bone under varied loading rates.

Bone tissue functions in varied mechanical systems of the body under static and dynamic conditions. Therefore, it is essential to understand the mechanical responses of bone at varied loading rates, especially those at fast loading rates. This study has investigated the effect of loading rate on the compressive mechanical properties of bovine cortical bone. Bone specimens of 3.85 mm in diameter and 7.7 mm in length were compressed longitudinally with the loading rates of 2 to 2000 mm/s (corresponding strain rates of 0.26 to 260 s(-1)). As a result, bovine cortical bone showed high linear elasticity when the loading rate was slow, and exhibited three definite regions of linear elasticity, plastic deformation, and densification at faster loading rates. The elastic modulus showed no dependency on the loading rate. Compressive strength, strain at fracture, and toughness increased as the loading rate increased under the condition that the loading rates were slower than each critical loading rate of 1000, 100, and 1500 mm/s, respectively. However, all showed no significant changes when the loading rates were faster than the corresponding critical loading rates. In conclusion, as the loading rate increased, changes in the compressive mechanical parameters were different depending on the parameter and the loading rate range. Compressive mechanical behaviour of bovine cortical bone showed a brittle nature under high strain rates (strain rates > 13 s(-1)). These findings should be reflected in the biomimetic simulation of biomaterials for bone tissue repair and engineering.

Primary transpupillary thermotherapy for small choroidal melanomas.

AIMS: To determine visual and anatomic outcomes following transpupillary thermotherapy (TTT) as a primary treatment for small choroidal malignant melanomas. METHODS: 20 patients with small choroidal melanomas who underwent primary TTT at our institution were retrospectively reviewed. Patients with choroidal melanomas posterior to the equator with a basal diameter less than 12 mm and thickness less than 3.5 mm were included if the lesion had documented growth or clinical risk factors for growth. RESULTS: Thirteen women and seven men (mean age: 65 years, range: 41-85 years) underwent TTT. The mean preoperative tumour thickness was 1.81 mm (range: 0.78-3.40 mm). The mean follow-up time after TTT was 44.6 months (range: 11-108 months, median: 47.5 months). After a mean of 2.15 primary TTT sessions (range: 1-4), tumour regression without recurrence was attained in 11 (55%) of 20 cases. Five of the nine remaining tumours with recurrence were successfully treated with additional TTT. One patient declined further TTT and underwent enucleation. Three other tumours had recurrence after repeat TTT. The mean time to recurrence after initial TTT was 20.8 months (range: 8-37 months). The mean time to recurrence after repeat TTT was 35 months (range: 5-69 months). There was no tumour-related metastasis or death. CONCLUSIONS: Tumours treated with TTT have significant recurrence rates. Although tumour control may ultimately be achieved with TTT, close monitoring of these tumours is necessary, since repeat TTT or alternative therapies may be required.

Early onset vitreous amyloidosis in familial amyloidotic polyneuropathy with a transthyretin Glu54Gly mutation is associated with elevated vitreous VEGF.

AIM: To report the early vitreous involvement in a rare familial amyloidotic polyneuropathy (FAP) mutation and associated vitreous vascular endothelial growth factor (VEGF) levels. DESIGN: Observational case series. METHODS: Review of clinical, pathological, photographic, and angiographic records of two FAP siblings with severe vitreous involvement. Laboratory ELISA analysis of vitreous samples for VEGF, and DNA sequence analysis of peripheral blood for transthyretin (TTR) mutational analysis. RESULTS: Two patients underwent 25-gauge vitrectomy in three eyes with marked improvement of visual acuity. Neovascularisation seen intraoperatively responded to endolaser. Analysis of vitrectomy samples for VEGF showed raised levels in all three specimens. Mutational analysis revealed an isolated Glu54Gly mutation in the transthyretin gene. CONCLUSIONS: Early involvement of the vitreous occurs in a rare transthyretin mutation of FAP, with increased vitreous levels of VEGF.

An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats.

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

Exudative retinal detachment in relapsing polychondritis : case report and literature review.

OBJECTIVE: To report the atypical ocular symptoms (arterialized conjunctival vessels, exudative retinal detachment) that can be the presenting manifestations of relapsing polychondritis. DESIGN: Observational case report and literature review. METHODS: A complete ocular and systemic evaluation was performed on a patient with relapsing polychondritis and exudative retinal detachment. MAIN OUTCOME MEASURES: Retinal, choroidal, and scleral findings. RESULTS: A 73-year-old man with relapsing polychondritis presented with a unilateral large bullous exudative retinal detachment and marked choroidal and scleral thickening bilaterally. CONCLUSIONS: Ophthalmologists should consider relapsing polychondritis in the differential diagnosis of exudative retinal detachment. A combination of echographic and laboratory findings can assist in the accurate diagnosis of this rare condition.

Angiopoietin-1 upregulation by vascular endothelial growth factor in human retinal pigment epithelial cells.

PURPOSE: To determine whether vascular endothelial growth factor (VEGF) regulates angiopoietin (Ang)-1 and -2 expression in retinal pigment epithelial (RPE) cells. METHODS: Expression of VEGF, Ang1, and Ang2 in surgically removed human choroidal neovascular membranes (CNVMs) was analyzed by double-label confocal immunofluorescence microscopy. Total RNA was extracted from cultured human RPE cells treated with VEGF for mRNA analysis. Northern blot analysis was performed to examine the time course and dose response of Ang1 and Ang2 mRNA expression. mRNA stability and nuclear run-on analyses were performed. Secreted Ang1 and Ang2 protein levels in conditioned media from RPE cells were examined by Western blot analysis. RESULTS: Ang1 and Ang2 immunostaining colocalized with VEGF-positive stromal cells in human CNVMS: Ang1 and Ang2 mRNAs were expressed by cultured serum-starved RPE cells. VEGF upregulated Ang1 mRNA in a time- and dose-dependent manner without a significant change in Ang2 mRNA. Ang1 and Ang2 mRNAs in RPE cells were as stable as that of S18. VEGF stimulation further increased the half-life of Ang1 mRNA, but did not alter its transcription rate. VEGF increased the amount of Ang1, but not Ang2, protein secreted into the medium. CONCLUSIONS: The colocalization of Ang1 and Ang2 with VEGF in CNVM stromal cells and the upregulation of Ang1 expression by VEGF in cultured RPE cells suggest that VEGF may selectively modulate Ang expression during CNV.

An ICG angiogram-based clinical method for characterizing the choroidal circulation used to assess the hemorrheologic effects of pentoxifylline.

PURPOSE: To demonstrate an indocyanine green (ICG) angiography-based clinical method for characterizing choroidal blood flow and for detecting changes in choroidal circulation patterns, and by use of that method, to demonstrate that pentoxifylline affects choroidal blood flow. METHODS: High-speed ICG angiography was performed in rhesus monkeys before and after intravenous administration of pentoxifylline or saline (which served as a control) while monitoring blood pressure and heart rate. From these data, three-dimensional surface maps indicating the instantaneous relative distribution of choroidal blood flow during the peak of intra-ocular pressure pulse systole in a 30 degrees field, centered on the macula, were generated to characterize the state of the choroidal circulation at various times during the experiments. RESULTS: Comparisons of the 3-dimentional surface maps consistently indicated an increase in sub-macular choroidal blood flow occurring within 5 to 10 minutes post-pentoxifylline injection, with a gradual return to baseline level 20-40 minutes later. Injection of equal volumes of saline produced no changes in choroidal blood flow. CONCLUSIONS: Posterior-pole choroidal blood flow can be characterized as by a three-dimensional surface representing the instantaneous relative distribution of choroidal blood flow during the peak of intra-ocular pressure pulse systole. Pentoxifylline does, at least transiently, increase sub-macular choroidal blood flow.

Radioactive plaque therapy for metastatic choroidal carcinoma.

PURPOSE: To describe the outcome of radioactive episcleral plaque therapy for treatment of metastatic carcinoma to the choroid. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Five patients (six eyes) with carcinoma metastatic to the choroid. METHODS: Retrospective review of the clinical records of five patients (six eyes) who underwent radioactive episcleral plaque therapy for choroidal metastases. MAIN OUTCOME MEASURES: Tumor height, visual acuity, radiation optic neuropathy, and radiation retinopathy. RESULTS: Radioactive episcleral plaque therapy resulted in shrinkage of the treated tumors and resolution of subretinal fluid in all eyes. After plaque treatment, best-corrected visual acuity was maintained within two lines of initial visual acuity for two eyes, decreased more than two lines for one eye, and improved more than two lines in three eyes. The treatment was well tolerated and there was no acute toxicity. Late complications included optic nerve atrophy (at 2 years) with proliferative radiation retinopathy (at 3 years) in one eye and optic atrophy (at 6 months) in another eye that had received prior external beam therapy. CONCLUSIONS: In carefully selected cases, radioactive episcleral plaque therapy appears to be an effective and reasonable treatment for carcinoma metastatic to the choroid.

Vitreoretinal surgery through multifocal intraocular lenses compared with monofocal intraocular lenses in fluid-filled and air-filled rabbit eyes.

PURPOSE: To compare vitrectomy procedures and visualization of posterior segment structures through multifocal silicone intraocular lenses (IOLs) with the same procedures through monofocal silicone IOLs in rabbit eyes. DESIGN: Experimental study. PARTICIPANTS: Twelve eyes of six rabbits. METHODS: Each rabbit eye underwent phacoemulsification of the lens and posterior chamber implantation of a silicone multifocal or silicone monofocal IOL. The type of IOL (monofocal vs. multifocal) implanted in the first eye of each rabbit was randomly decided. The fellow eye then received the other IOL type. Vitrectomy procedures were performed through the IOLs by using a flat contact lens (part 1) or wide-angled contact lens (part 2) for visualization through fluid-filled (parts 1 and 2) and air-filled (part 2) eyes. MAIN OUTCOME MEASURES: Image quality, stereopsis, and contrast were subjectively graded on a scale of 0 (none) to 4 (excellent) for each eye by each surgeon. RESULTS: In part 1, image quality averaged 4 for the monofocal IOL and 3.6 for the multifocal IOL. Stereopsis averaged 4 for the monofocal IOL and 4 for the multifocal IOL. Contrast averaged 4 for the monofocal IOL and 3.9 for the multifocal IOL. Vitrectomy with retinal surface maneuvers was successfully performed in both pigmented and nonpigmented rabbit eyes through both IOL types. In part 2, image quality, stereopsis, and contrast were rated as 4 for both multifocal and monofocal silicone IOLs. Air-fluid exchange was performed without difficulty. Image quality, stereopsis, and contrast were rated as 4 for air-filled eyes. CONCLUSIONS: Visualization of posterior segment structures through multifocal silicone IOLs was sufficient for retinal surface maneuvers during vitrectomy procedures in both fluid-filled and air-filled rabbit eyes.

A comparison of digital nonmydriatic fundus imaging with standard 35-millimeter slides for diabetic retinopathy.

PURPOSE: The purpose of this study was to compare nonmydriatic digital images with 35-mm slide images for the detection of diabetic retinal findings. STUDY DESIGN: Comparative, observational case series. PARTICIPANTS: Twenty-two patients with diabetes. METHODS: Diabetic patients underwent digital (nonmydriatic fundus camera attached to a digital back) and standard dilated 35-mm retinal photography of three areas: posterior pole, nasal retina, and temporal retina. The images were reviewed by a single masked grader for the presence or absence of specific retinal findings. PRIMARY OUTCOME MEASURES: Presence or absence of neovascularization of the disc (NVD), neovascularization elsewhere (NVE), venous beading (VB), nerve fiber layer (NFL) hemorrhage, dot-blot hemorrhage, microaneurysm (MA), clinically significant macular edema, cotton wool spot, intraretinal microvascular anomaly (IRMA), hard exudate (HE), and retinal pigment epithelial (RPE) pigmentary changes. RESULTS: Forty eyes of 22 patients underwent both imaging procedures. The agreement between image type was highest for IRMA (97.5%) and VB (95%) and lowest for RPE pigmentary changes (65%) and MA (62.5%). Sensitivity ranged from 25% (NVD) to 100% (VB). Specificity ranged from 90% (RPE pigmentary changes) to 100% (NVD, NVE, VB, NFL hemorrhage, HE). Positive predictive value ranged from 50% (IRMA) to 100% (NVD, NVE, HE, NFL, VB). Negative predictive value ranged from 48% (MA) to 100% (IRMA). CONCLUSIONS: Nonmydriatic digital fundus imaging for detection of diabetic retionopathy has a low sensitivity rate and a high specificity rate and is less clinically useful than standard dilated 35-mm fundus slide images.

Iatrogenic choroidal neovascularization.

Iatrogenic choroidal neovascularization is an uncommon complication of laser photocoagulation and other ocular surgical procedures. It appears to be the result of a number of conditions, including damaged Bruch's membrane and/or retinal pigment epithelium, whose reparative processes trigger the release of angiogenic factors. Inflammatory cells and choroidal ischemia may also play a role. The prognosis varies depending on the underlying disease and the type of choroidal neovascularization (subretinal, chorioretinal, or choriovitreal). Minimizing the amount of laser energy used during laser procedures, avoiding repeat laser treatment to the same retinal area, and minimizing direct mechanical trauma to the retinal pigment epithelium and choroid decrease the chance of inducing iatrogenic choroidal neovascularization.

Multiple evanescent white dot syndrome in older patients.

PURPOSE: To report two patients in their seventh decade who exhibited findings consistent with multiple evanescent white dot syndrome. METHODS: Case reports of two patients referred for evaluation of decreased vision, visual field loss, and retinal white spots. RESULTS: A 60-year-old man and a 67-year-old woman had photopsia, visual field loss, and decreased central visual acuity. Examination disclosed numerous white retinal spots, ranging from 50 to 400 microm, with eventual foveal granularity. Visual field testing showed an enlarged blind spot and peripheral field defects. Fluorescein angiography, electroretinography, and electrooculography results were consistent with multiple evanescent white dot syndrome. Eventually, the retinal lesions resolved in both patients and baseline visual acuity was recovered. CONCLUSION: A diagnosis of multiple evanescent white dot syndrome should be considered in patients with retinal findings typical of multiple evanescent white dot syndrome, regardless of age.

Visual and anatomic outcomes associated with posterior segment complications after ganciclovir implant procedures in patients with AIDS and cytomegalovirus retinitis.

PURPOSE: To determine anatomic and visual acuity outcomes of posterior segment complications after ganciclovir implant surgery. METHODS: We reviewed the medical records of 63 patients with acquired immunodeficiency syndrome who had active cytomegalovirus retinitis in 82 eyes and who underwent 110 consecutive ganciclovir implant procedures. Preoperative and postoperative visual acuity, type of postoperative complication, treatment, and lines of visual acuity change were determined. RESULTS: Thirty-eight eyes of 19 patients had bilateral ganciclovir implant procedures, and 25 eyes of 19 patients underwent two or more ganciclovir implant procedures. Thirteen (12%) of 110 ganciclovir implant procedures developed posterior segment complications: rhegmatogenous retinal detachment in six, vitreous hemorrhage in four, endophthalmitis in two, and cystoid macular edema with epiretinal membrane in one. Treatment included pars plana vitrectomy with silicone oil in two cases and without silicone oil in three cases, scleral buckling in one, intravitreal antibiotic injection in two, and laser photocoagulation in two. Overall, median visual acuity was 20/25 preoperatively. Median follow-up was 6 months for all eyes and 7 months for eyes with complications. Postoperative median visual acuity was 20/25 for eyes without complications vs 20/40 at 1 month, 20/60 at 3 and 6 months, and 20/100 at 12 months in eyes with complications (P < .001). More eyes with than without complications lost 2 or more lines of visual acuity (P < .001). CONCLUSION: Postoperative complications occurred in 12% of the ganciclovir implant procedures and were associated with decreased visual acuity despite treatment.

Symptomatic age-related macular degeneration in Asian patients.

PURPOSE: To characterize retinal and fluorescein angiographic findings of Asian patients with symptoms secondary to age-related macular degeneration (ARMD). METHODS: We retrospectively reviewed 453 consecutive medical records corresponding to fluorescein angiograms performed between November 1992 and November 1995 to identify Asian patients with symptomatic ARMD. Presenting visual symptoms, best-corrected Snellen visual acuities, and retinal examination findings were determined from the medical records. Fundus photos and fluorescein angiograms were reviewed. RESULTS: There were 26 symptomatic eyes in 19 Asian patients with a median age of 73 years. Presenting visual symptoms included decreased visual acuity (19 eyes), metamorphopsia (5 eyes), or scotoma (2 eyes). Retinal findings included occult choroidal neovascularization (CNV) in 5 (19%) eyes, serous pigment epithelial detachment (PED) in 8 (31%) eyes, PED with CNV in 5 (19%) eyes, drusen in 5 (19%) eyes, retinal pigment epithelial atrophy in 1 (4%) eye, vitreous hemorrhage in 1 (4%) eye, and a disciform scar in 1 (4%) eye. CONCLUSION: In this cohort of Asian patients with ARMD, the majority of symptomatic eyes had either CNV (46%) or serous PED (31%).