A novel eye drop application monitor to assess patient compliance with a prescribed regimen: a pilot study.

PURPOSE: To assess the ability of a novel imaging device to allow physicians to personalize therapeutic regimens based on objective patient drop administration data. METHODS: A novel imaging system was used to record video of the drop technique of subjects in clinic (n=25) or at home (n=17) for 1 week. Video assessment by a reading center was compared with patient reporting and their prescribed regimen with respect to how many drops were applied and how many landed in the eye. RESULTS: Reading center assessment of both drops dispensed and drops landing in the eye was significantly different from the prescribed regimen in the clinic (Pd=0.005, Pi<0.001, respectively) and at-home arms (Pd=0.003, Pi<0.001, respectively). CONCLUSIONS: This imaging system is a powerful tool to help physicians tailor patient therapy more accurately, to help researchers evaluate new drop therapies with objective rather than subjective data, and to potentially facilitate better patient training for improved drug delivery.

Residual edema evaluation with ranibizumab 0.5 mg and 2.0 mg formulations for diabetic macular edema (REEF study).

PURPOSE: To compare the efficacy of ranibizumab 0.5-mg and 2.0-mg intravitreal injections for persistent diabetic macular edema (DME) previously treated with bevacizumab. METHODS: In all, 43 patients with residual center-involved DME following intravitreal bevacizumab were included in this 12-month prospective, nonrandomized, multicenter study. Enrolled patients received three monthly ranibizumab 0.5-mg injections. At month 3, patients with residual macular edema switched to three monthly injections of ranibizumab 2.0-mg. Assessments included monthly visual acuity and spectral-domain optical coherence tomography. RESULTS: Mean visual acuity improved by +6.4 letters at month 3 and +8.8 letters at month 6. Mean central subfield thickness (CST) decreased by -113 µm at month 3 and -165 µm at month 6. Before enrollment, 29/43 (67.4%) patients showed <10% CST reduction following monthly bevacizumab treatment. After three monthly ranibizumab 0.5-mg injections, 22/29 (75.9%) patients showed >10% reduction in CST, whereas 6 showed <10% reduction. Of these six, three (50%) showed >10% reduction in CST after switching to three monthly ranibizumab 2.0-mg doses. No serious adverse events were observed to month 6. CONCLUSION: Ranibizumab 0.5-mg or 2.0-mg may improve visual and anatomic outcomes in patients with DME who demonstrated minimal or no response to bevacizumab therapy. Moreover, increased dosage of ranibizumab (2.0-mg) may provide additional benefit over ranibizumab 0.5-mg in some patients. However, 2.0-mg ranibizumab is not currently commercially licensed or available.

Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy.

AIMS: The aim of this study was to report the development or progression of tractional retinal detachment (TRD) after the injection of intravitreal bevacizumab (Avastin) used as an adjuvant to vitrectomy for the management of severe proliferative diabetic retinopathy (PDR). METHODS: The clinical charts of patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 mg bevacizumab before vitrectomy for the management of PDR were reviewed. RESULTS: Eleven eyes (patients) out of 211 intravitreal injections (5.2%) that developed or had progression of TRD were identified. All eyes had PDR refractory to panretinal photocoagulation (PRP). Nine patients had type 1 diabetes mellitus (DM), and two patients had type 2 DM. Patients had a mean age of 39.5 years (range 22-62 years). In the current study, all patients used insulin administration and had poor glycaemic control (mean HbA(1c) 10.6%). Time from injection to TRD was a mean of 13 days (range 3-31 days). Mean best correct visual acuity (BCVA) at TRD development or progression was logarithm of the minimal angle of resolution (LogMAR) 2.2 (range 1.0-2.6) (mean Snellen equivalent hand motions; range 20/200 to light perception), a statistically significant worsening compared with baseline BCVA (p<0.0001). Eight eyes underwent vitrectomy and three patients refused or were unable to undergo surgery. The final mean BCVA after surgery was LogMAR 0.9 (range 0.2-2.0) (mean Snellen equivalent 20/160; range 20/32 to counting fingers), a statistically significant improvement compared with TRD BCVA (p = 0.002). CONCLUSIONS: TRD may occur or progress shortly following administration of intravitreal bevacizumab in patients with severe PDR.

Initial experience with pneumatically stented baerveldt implant modified for pars plana insertion for complicated glaucoma.

OBJECTIVE: To assess the efficacy of pneumatically stented drainage tube implants specially modified for pars plana insertion in the treatment of complicated glaucoma. DESIGN: Retrospective, non-comparative case series. PARTICIPANTS: 50 consecutive patients with refractory complicated glaucoma nonresponsive to medical treatment. INTERVENTION: Baerveldt glaucoma implants modified by Hofmann for pars plana insertion were placed following pars plana vitrectomy and gas-fluid exchange (pneumatically stented implant, or PSI procedure). MAIN OUTCOME MEASURE: Reduction of intraocular pressure (IOP) to 21 mmHg or less. RESULTS: 31 neovascular and 19 complicated non-neovascular glaucoma eyes in 48 patients referred to a vitreoretinal subspecialty practice, average age 69 years (range 29-91), were followed an average of 18 months (range 3-41). The average preoperative IOP was 44 mmHg (14-78) on an average 3.2 glaucoma medications (range 2-6). The average final postoperative IOP was 14 mmHg (range 5-31) on an average 0.6 glaucoma medications (range 0-3, median 0). The final intraocular pressure was 21 mmHg or less in 47 of 50 (94%) operated eyes. Serious complications related to the procedure occurred in five eyes (10%). CONCLUSIONS: Pneumatically stented Baerveldt glaucoma implants modified with the Hofmann elbow to facilitate pars plana insertion are effective in the treatment of complicated glaucoma.

Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration.

PURPOSE: The authors describe the natural history of subfoveal subretinal hemorrhage (for which laser treatment was not indicated) in age-related macular degeneration. METHODS: A retrospective review of data was performed at a tertiary retinal referral center for 41 eyes from 40 patients with age-related macular degeneration examined during an 18-month period. All patients had at least 3 months of follow-up, as well as subfoveal subretinal hemorrhage that made up more than 50% of a neovascular lesion-as documented by fluorescein angiography-and therefore, did not meet criteria for laser treatment. The number of lines of visual acuity lost or gained in each eye during follow-up was calculated; presenting characteristics were evaluated as predictors of visual outcome. RESULTS: A progressive loss of visual acuity from baseline was observed throughout the 3-year follow-up period in most eyes. At 36 months, a mean of 3.5 lines of visual acuity had been lost in the 16 eyes examined; 44% of eyes had lost 6 or more lines of visual acuity. The percentage of patients who sustained a spontaneous improvement of 3 or more lines of visual acuity decreased from 31% at 12 months to 21% at 36 months of follow-up. Univariate linear regression analysis demonstrated significant relationships of initial size of the hemorrhage, elevation of the retina by the hemorrhage, and size of the entire lesion with visual outcome at the 12-month and 36-month examinations (P < 0.05). CONCLUSIONS: Although this study confirms that some eyes with subfoveal subretinal hemorrhage associated with age-related macular degeneration have poor prognoses, the visual acuity of other eyes did not deteriorate. These findings underscore the importance of evaluating the role of therapeutic interventions such as surgery to remove subretinal hemorrhage in randomized clinical trials.

Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization.

Neovascular diseases of the retina are a major cause of blindness worldwide. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, but the factors involved in the hypoxic neovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VPF mRNA and protein were studied in a mouse model of proliferative retinopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF mRNA expression increased 3-fold between 6 and 12 hr of relative retinal hypoxia and remained elevated during the development of neovascularization. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclear layer of the retina that produce VEGF/VPF were identified morphologically as Müller cells. These data suggest that VEGF/VPF expression in the retina plays a central role in the development of retinal ischemia-induced ocular neovascularization.

Pars plana implant and vitrectomy for treatment of neovascular glaucoma.

PURPOSE: To evaluate the effectiveness of pars plana implants in the treatment of neovascular glaucoma. PATIENTS AND METHODS: Twenty-two consecutive pars plana implant procedures performed for neovascular glaucoma were retrospectively reviewed. RESULTS: Preoperative intraocular pressures ranged from 22 to 80 mmHg (mean 46 mmHg) on a mean of three glaucoma medications. With a mean follow-up interval of 16 months, final postoperative intraocular pressures ranged 9-21 mmHg (mean 16) on a mean 0.7 medications. One patient required a second implant to achieve final intraocular pressure control. Visual acuity was stabilized or improved in 19 of 22 cases (86%). Complications included retinal detachment in two cases (9%). Macular pucker, vitreous hemorrhage, hyphema, choroidal hemorrhage, diplopia, and loss of light perception occurred in one case (5%) each. None developed phthisis bulbi. CONCLUSION: Pars plana drainage tube implants are effective in the treatment of neovascular glaucoma.

Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.

BACKGROUND: Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. METHODS: We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmuno-assays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. RESULTS: VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P < 0.001, P < 0.001, and P = 0.006, respectively). The mean (+/- SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 +/- 6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 +/- 0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2 +/- 0.6 ng per milliliter, P < 0.001), or 31 samples from nondiabetic patients (0.1 +/- 0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8 +/- 9.9 ng per milliliter) were higher than those in aqueous fluid (5.6 +/- 8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. CONCLUSIONS: Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.

Suture abscesses after penetrating keratoplasty.

Eighteen suture abscesses that developed after penetrating keratoplasty in 15 patients were reviewed. The time from keratoplasty to the diagnosis of an abscess ranged from 1 to 53 months with a mean of 21.5 months. In 13 of the 18 cases, the patient was taking topical steroids at the time of diagnosis. All were culture-proven bacterial ulcers, except for one case that had a positive Gram's stain, but no growth on culture. The organisms cultured were Staphylococcus epidemidis (six eyes), Streptococcus pneumoniae (five eyes), Sta. aureus (four eyes), Str. viridans (two eyes), Klebsiella oxytoca (one eye), Serratia marcescens (one eye), Moraxella sp (one eye), and Escherichia coli (one eye). The offending suture was removed in all cases, and the eyes were treated with topical fortified antibiotics (cefazolin and tobramycin). After treatment, 67% (12 of 18 eyes) had clear grafts, 17% (three of 18 eyes) were scarred, and 16% (three of 19 eyes) had failed grafts. Intensive topical steroid therapy was used when a subsequent graft rejection developed. Retained sutures following corneal transplants can result in sight-threatening infections and should be considered for removal as soon as the wound is well healed.

Systemic amiloride inhibits experimentally induced neovascularization.

Amiloride is an inhibitor of urokinase-type plasminogen activator, and might therefore have an inhibitory effect on neovascularization. Neovascularization was induced in rabbit corneas via local implantation of prostaglandin E1 pellets prepared in a slow-release polymer. Animals received daily intraperitoneal injections of 30 mg of amiloride, or an equivalent volume of saline solution for 5 days; both were well tolerated without severe untoward effect. Neovascular response, as documented by corneal photographs, was evaluated after 5 days of injections. The area of induced corneal neovascularization was decreased by 55% in animals receiving amiloride when compared with controls. Thus, amiloride and similar compounds may prove useful in the study and management of neovascularization.

Inhibition of retinal pigment epithelial cell attachment by a synthetic peptide derived from the cell-binding domain of fibronectin.

Retinal pigment epithelial (RPE) cells are dispersed into the vitreous cavity during retinal reattachment surgery and attach to the vitreous gel and internal limiting membrane. Subsequent migration and cell-mediated contraction can result in traction retinal detachment. Fibronectin (FN) can enhance the attachment of various cell types. We now report that FN enhances the attachment of human and porcine RPE cells. A synthetic tetrapeptide, arg-gly-asp-ser (RGDS), derived from the FN cell-binding domain, has been shown to interfere with attachment of some cell types. We now report that RGDS inhibits RPE cell attachment to FN in a dose-dependent manner with 70% inhibition at 1 mg/mL. Also, RGDS inhibits attachment to types I and II collagen, as well as to lens capsule basement membrane by 40%, 50%, and 25%, respectively. Therefore, RGDS or its derivatives may have some eventual role in the management of proliferative vitreoretinopathy.