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William R Freeman

Publications and source records attributed to William R Freeman.

At least 37 records · Page 2Linked to original sources

Scanning laser entoptic perimetry for the detection of age-related macular degeneration.

OBJECTIVE: To determine the sensitivity and specificity of scanning laser entoptic perimetry for detecting visual function damage due to age-related macular degeneration (ARMD). METHODS: We measured the presence or absence of visual field disturbances by entoptic perimetry and determined the severity of ARMD based on masked readings of fundus photographs. A prospective masked study comparing the findings of entoptic perimetry with fundus photographs was performed. We recruited 91 patients with ARMD and 24 patients without ARMD during ophthalmologic visits. An appropriate institutional review board approval was obtained for the project. The main outcome measure was the detection of visual scotomata. RESULTS: Scanning laser entoptic perimetry had an overall sensitivity of 82% and a specificity of 100% for the detection of ARMD. The sensitivity for early stages of the disease is greater than 70%, and increases to above 90% for moderate to late stages. CONCLUSION: Scanning laser entoptic perimetry is a specific and sensitive test for detecting ARMD, even at the earliest stages when patients are typically asymptomatic.

Aged↗

Valganciclovir therapy for immune recovery uveitis complicated by macular edema.

PURPOSE: To determine whether treatment with valganciclovir will improve visual acuity in eyes with immune recovery uveitis complicated by macular edema. DESIGN: Prospective open label controlled Phase II drug study. METHODS: Five patients with chronic macular edema as a result of immune recovery uveitis were studied. Baseline fluorescein angiograms, best-corrected ETDRS visions, and cytomegalovirus (CMV) lymphoproliferative T-cell function assays were obtained and repeated after three months of valganciclovir therapy (900 mg daily) and again three months after withdrawal of therapy. RESULTS: Vision improved by a mean of 11 letters in the treatment phase (P =.05). Graded angiograms showed three patients had treatment reduction of macular edema. One patient had rebound increase in macular edema after the withdrawal phase. The CMV lymphoproliferative response was not affected by the valganciclovir. CONCLUSION: Results suggest valganciclovir treatment may benefit visual acuity in patients with macular edema from immune recovery uveitis.

AIDS-Related Opportunistic Infections↗

The relationship between AIDS retinal cotton wool spots and neuropsychological impairment in HIV-positive individuals in the pre-highly active antiretroviral therapy era.

PURPOSE: To determine the relationship between AIDS retinal cotton wool spots (CWS) and neuropsychological impairment in HIV-positive individuals in the pre-HAART (highly active anti-retroviral therapy) era and the association between AIDS-related retinal CWS and neuropsychological impairment in HIV-positive patients not treated with HAART. METHODS: A case-control analysis of prospectively acquired data in HIV-infected individuals who underwent prospective and longitudinal evaluations of retinal findings as well as neuropsychological testing was performed. Individuals underwent prospective retinal ophthalmic examinations with fundus photography of any retinal lesions. They also underwent periodic neuropsychological testing. The occurrence of retinal CWS was analyzed in relationship to neuropsychological impairment. RESULTS: Thirty individuals with CWS were compared to 6o matched control AIDS patients. There was no association between either global clinical neuropsychological impairment or impairment in any of the five major domains tested and retinal CWS. There was an association between beta-2 microglobulin and CWS as well as an association between low CD4 T-cell count and the presence of retinal CWS. CONCLUSIONS: We found no association between retinovascular disease and neurocognitive impairment in this case-control study. Retinal CWS in HIV disease are related to higher serum beta-2 microglobulin levels and lower CD4 T-cell counts, suggesting that these lesions are related to HIV disease progression but may be caused by a pathological process independent of CNS disease.

AIDS Dementia Complex↗

Preventive versus treatment effect of AG3340, a potent matrix metalloproteinase inhibitor in a rat model of choroidal neovascularization.

PURPOSE: AG3340 (prinomastat) is a nonpeptidic, small-molecular-weight, synthetic matrix metalloproteinase inhibitor (MMPI) with selective inhibitory action of MMP-2, MMP-9, MMP-3, and MT-MMP1. We evaluated AG3340 injected intravitreally to treat choroidal neovascularization in a laser induced rat CNV model. METHODS: In the pretreatment group, the drug was injected the same day after induction of choroidal neovascularization by diode laser. In the treatment group, the drug was injected 2 weeks after induction of choroidal neovascularization (CNV). Fluorescein and indocyanine green angiography were performed to evaluate CNV. ERG recordings and histology were performed to assess toxicity and the CNV lesions. RESULTS: When used at the time of CNV induction, 62.8% of lesions in control versus 22.8% of the laser lesions in treated eyes developed CNV (p < 0.0001). The invading fibrovascular complex was thicker in the control eyes than that in the treated eyes. No signs of toxicity were detected. When used to treat established CNV, the percentage of leakage in treated and control eyes were 54.1% and 58.9% respectively (p > 0.05). Prinomastat was effective when given at the time of induction of CNV in the rat model. Administration of prinomastat 2 weeks after laser induction did not show efficacy. CONCLUSION: Prinomastat was active in the earliest stages of experimental CNV. It might be best used in combination with photodynamic therapy to inhibit recurrence of CNV from temporarily closed new vessels.

Animals↗

Intraocular properties of urokinase-derived antiangiogenic A6 peptide in rabbits.

To investigate the intraocular properties of an antiangiogenic peptide, A6, a total of 70 New Zealand rabbit eyes were used. For the toxicity study, 0.05 mL of 0.459 M or 0.148 M A6 was injected intravitreally; right eyes received A6, and left eyes received a vehicle. Serial intraocular pressure measurement, slit lamp, and indirect ophthalmoscopy were performed. The rabbit eyes were evaluated by fluorescein angiography, electroretinography, and histology after the scheduled sacrifice. The pharmacokinetics of an intravitreal A6 (0.05 mL of 0.488 M) and a subtenon A6 (0.5 mL of 0.305 M) injection was studied. There was no toxicity observed following the 0.148 M A6 intravitreal injections. In 2 eyes with a 0.459 M A6 intravitreal injection, focal retinal pigmentary change was observed at the injection site, which was contacted by the hyperosmolar drug bolus. Choroidal A6, following the intravitreal injection, remained therapeutic (>or=10 microM) for 72 hours. The vitreous half-life was 19.4 hours. Choroidal concentrations following the subtenon injection were minimal. The low choroidal concentrations observed may relate to the polar nature of A6. More hydrophobic analogs of A6 are likely to cross the retina more efficiently. However, in diseased eyes, in the area of choroidal neovascularization (CNV), the fluid-filled, damaged, edematous retina may permit the drug to enter the choroid in higher concentrations.

Angiogenesis Inhibitors↗

Long-term results of treatment of macular complications in eyes with immune recovery uveitis using a graded treatment approach.

PURPOSE: To evaluate the results of a graded treatment approach in a cohort of eyes with macular complications of immune recovery uveitis. METHODS: A cohort of 18 eyes of 13 patients representing all eyes with these complications at the University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes were classified into three groups and treated according to a graded protocol. RESULTS: Eyes with mild disease (macular edema and vision of 20/30 or better) were observed. These six eyes maintained good vision with only one dropping to 20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of 9 patients), repository sub-Tenon steroid injections were used repeatedly. There were no complications of steroid use but visual improvement occurred in only 40% of eyes. Macular edema persisted. In eyes with structural macular changes, such as epiretinal membrane, vitrectomy resulted in vision improvement in three of four eyes. The cystoid macular edema persisted despite surgery. CONCLUSION: Mild cases of immune recovery uveitis and macular edema may be observed. In eyes with reduction of vision due to cystoid macular edema, there was only a modest treatment effect using repository corticosteroids. Eyes with immune recovery uveitis that develop epiretinal membrane undergo some visual improvement after removal of the membrane. The macular edema of immune recovery uveitis is resistant to corticosteroid treatment.

AIDS-Related Opportunistic Infections↗

The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinase, on a new animal model of epiretinal membrane.

PURPOSE: To develop a simple epiretinal membrane (ERM) animal model and evaluate the efficacy of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinase. METHODS: This experiment was carried out on 18 eyes of nine Brown Norway rats. Preretinal hemorrhage was induced bilaterally using diode laser focused deeply on choroidal blood vessels. One day later, AG3340 was injected intravitreally in the right eyes while the left eyes received equal amounts of vehicle. The developed epiretinal membrane was measured in disk areas and compared between groups. RESULTS: Clinically, preretinal hemorrhage showed a slow clearance persisting for 8 to 10 weeks. ERM was well established around 12 weeks. Histologically, ERMs consist of fibroblast and glial cells embedded in collagen-rich extracellular matrix infiltrated by macrophages. Seventy-five percent of the hemorrhagic laser burns in the control group developed ERM, whereas only 25% of the hemorrhagic laser burns in treated group developed ERM (P = 0.01). The total surface area of developed ERM was 3.66 DD in treated eyes versus 25.45 DD in control eyes (P = 0.049). The mean surface area of ERM per eye was 0.52 disk areas +/- 1.05 in treated eyes versus 3.18 +/- 3.07 in control eyes. CONCLUSION: We demonstrated that ERM can be induced on rat retina by simple hemorrhagic retinal laser coagulation. This new animal model could be used for future evaluation of different medical treatment modalities for proliferating ERM. Furthermore, AG3340 demonstrated an inhibitory effect on ERM formation in this new rat model.

Animals↗

Inhibition of choroidal neovascularization in rats by the urokinase-derived peptide A6.

PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide A6 on laser-induced choroidal neovascularization (CNV). METHODS: In the first arm of the study, subcutaneous injection of A6 (200 mg/kg per day) into the right eyes in 20 rats and phosphate-buffered saline in 20 control rats was started 1 day before laser injury. Angiography was performed at week 2. To evaluate the dose response, a second arm of the study was performed in the left eyes. Half of the treatment group was treated with 400 mg/kg per day, and the remaining half continued to receive 200 mg/kg per day beginning on week 4. Laser injury was made at week 5 and angiography was performed at week 7. Angiographic evaluation, histopathologic evaluation including maximum CNV thickness and factor-VIII-stained endothelium counting were performed in the second arm of the study. Choroidal concentrations of A6 were measured. RESULTS: In the first arm of the study, angiography showed a 40.8% reduction in CNV in the 200-mg/kg per day treatment group, compared with the control (P = 0.0008). In the second arm of the study, angiographic reduction in CNV was 37.9% in the 200-mg/kg per day group (P = 0.0314) and 70.0% in the 400-mg/kg per day group (P = 0.0124), compared with the control. CNV was significantly less in the 400-mg/kg per day group than in the 200-mg/kg per day group (P = 0.0393). Both CNV thickness and number of endothelial cells were reduced in a dose-dependent manner and significantly less than in the control (P < 0.05). Mean choroidal concentration of A6 2 hours after injection was 0.72 micro M in the 200-mg/kg per day (100 mg/kg every 12 hours) and 1.75 micro M in the 400-mg/kg per day (200 mg/kg every 12 hours) treatment groups. Levels at 11 hours after injections were undetectable. CONCLUSIONS: A6 demonstrated antiangiogenic properties in a rat model of CNV and may be useful in the treatment of CNV.

Animals↗

Characterization of a novel intraocular drug-delivery system using crystalline lipid antiviral prodrugs of ganciclovir and cyclic cidofovir.

PURPOSE: In an earlier study, a novel intraocular drug-delivery system was reported in which hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV) was used as a prototype. The hypothesis was that many biologically effective compounds could be modified to crystalline lipid prodrugs and could be delivered directly into the vitreous in a long-lasting, slow-release form. This study was undertaken to characterize this new drug-delivery system further, by using small particles of HDP-P-GCV and hexadecyloxypropyl-cyclic cidofovir (HDP-cCDV). METHODS: HDP-P-GCV was microfluidized into 4.4-microm (median) particles, injected into rabbit vitreous. The vitreous drug level was then measured at different time points. Crystalline HDP-cCDV was synthesized, suspended in 5% dextrose, and injected into the rabbit's vitreous at 10, 55, 100, 550, or 1000 microg in 50 microL vehicle per eye, to determine the highest nontoxic dose. The dose, 100 microg, was injected into 24 rabbit eyes, to evaluate pharmacokinetics; into 14 rabbit eyes with established HSV retinitis, to evaluate its efficacy; and into 58 rabbit eyes before herpes simplex virus (HSV) infection to evaluate its intraocular antiviral duration. RESULTS: Microfluidized particles of HDP-P-GCV showed an increased drug release rate compared with the large-particle drug formulation, with area under concentration-time curve (AUC) of 219.8 +/- 114.1 (n=3) versus 108.3 +/- 47.2 (n=3) for unmodified HDP-P-GCV during the 12-week period after a 2.8-micromole intravitreal injection. There was a 103% increase of the drug released from the microfluidized formulation of HDP-P-GCV versus the unmodified formulation. Intravitreal injections of HDP-cCDV at doses of 100 microg/eye or lower were not toxic. After the 100 microg/eye injections, HPLC analysis showed a vitreous HDP-cCDV level of 0.05 microM at week 5, which declined to 0.002 microM at week 8. The concentration at week 8 (0.002 microM) remained above the IC50 for cytomegalovirus (0.0003 microM). The pretreatment study demonstrated an antiviral effect that lasted 100 days after a single intravitreal injection. CONCLUSIONS: This crystalline lipid prodrug intravitreal delivery system is an effective approach to achieving sustained, therapeutic drug levels in the eye. Small microfluidized particles of HDP-P-GCV provide more rapid dissolution and higher vitreous drug levels.

Animals↗

Volumetric analysis of macular edema by scanning laser tomography in immune recovery uveitis.

OBJECTIVES: To evaluate the macular volume in eyes with immune recovery uveitis (IRU) and to describe a new method to quantify macular edema with the use of confocal scanning laser tomography (cSLT). METHODS: A prospective study was performed to assess the macular volume with cSLT in patients with and without IRU. None of the patients enrolled had cytomegalovirus retinitis within 3000 micro m of the fovea. Eight eyes had healed cytomegalovirus retinitis with IRU and cystoid macular edema (group A); 4 eyes had healed cytomegalovirus retinitis with IRU and clinically normal maculas (group B); 18 eyes had no IRU (group C); and 3 eyes underwent pars plana vitrectomy and epiretinal membrane peeling for epiretinal membranes associated with cystoid macular edema and IRU (group D). Patients with IRU underwent standard clinical examinations and cSLT. On cSLT, volume above the reference plane was calculated within a fovea-centered circle of 3 mm in diameter. We devised a novel system for defining the reference plane. Measurements were performed 3 times in masked fashion and the mean was used for analyses. RESULTS: The mean macular volume was highest in group A (1.97 mm3). This was significantly higher (P<.001) than that in groups B (1.15 mm3), C (1.02 mm3), and D (0.86 mm3). CONCLUSIONS: Macular edema in patients with IRU can be consistently and objectively quantitated by cSLT. The method of defining the reference plane used in our study is novel and can be used in other disorders causing macular edema.

AIDS-Related Opportunistic Infections↗

Effect of anti-cytomegalovirus therapy on the incidence of immune recovery uveitis in AIDS patients with healed cytomegalovirus retinitis.

PURPOSE: To determine the association between anticytomegalovirus (CMV) maintenance therapy after immune recovery and immune recovery uveitis in acquired immunodeficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART). DESIGN: Observational cohort study. METHODS: Data were obtained on AIDS patients with CMV retinitis followed up at the AIDS Ocular Research Unit of University of California San Diego from November 1995 to October 1999. Immune recovery was defined as CD4 count greater than 50 cells/microl for more than 3 months. Patients with immune recovery uveitis presented with vitritis, cystoid macular edema, or epiretinal membrane. Statistical analyses were conducted to determine the risk of continued use of anti-CMV therapy after immune recovery and the relationship of developing immune recovery uveitis with the type of anti-CMV therapy. RESULTS: Forty-three patients (64 eyes) had healed CMV retinitis and had achieved immune recovery. Thirty-one patients (48 eyes) received anti-CMV therapy after immune recovery, and 20 patients (29 eyes) developed immune recovery uveitis. Per-eye analyses revealed a 3.8-fold increase in the odds of developing immune recovery uveitis with anti-CMV therapy compared with no treatment (P =.02). If treated with cidofovir the odds were 3.3 greater than if treated with an alternative regimen (P =.04), 4.1 greater if treated intravenously (P =.01), and 5.2 greater than if not treated (P =.004). If not treated with cidofovir, a nonsignificant increase in the risk (2.4) of immune recovery uveitis was found (P =.15). Neither the potency nor the use of implants for noncidofovir treatment was related to the risk of recovery uveitis (P >.62). CONCLUSIONS: The use of cidofovir is a primary risk factor in the subsequent development of immune recovery uveitis. Ongoing treatment of healed CMV retinitis after immune recovery does not appear to protect against the development of immune recovery uveitis.

AIDS-Related Opportunistic Infections↗

Ganciclovir release rates in vitreous from different formulations of 1-O-hexadecylpropanediol-3-phospho-ganciclovir.

PURPOSE: To determine the optimal formulation of lipid prodrug, 1-O-hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV), for intravitreal delivery. METHODS: Equal concentrations of crystalline or liposomal HDP-P-GCV were exposed to rabbit whole vitreous, core vitreous, peripheral vitreous, human plasma, and heat inactivated rabbit vitreous, and the samples were incubated at 37 degrees C for one week. Aliquots were taken at day 1, 2, 3, and 7 and subjected to HPLC analysis for conversion to GCV. RESULTS: The resultant concentration of GCV from crystalline HDP-P-GCV in vitreous was 198 +/- 49 microM (n = 3) at day 1 and 1253 +/- 248 microM (n = 3) at day 7. The resultant concentration of GCV from the liposomal formulation of HDP-P-GCV in vitreous was much lower, yielding a concentration of 66 +/- 7 microM (n = 3) at day 1 and 243 +/- 39 microM (n = 3) at day 7 (P < 0.001, t Test). When the crystalline HDP-P-GCV was incubated with heat-inactivated vitreous, the detectable GCV concentrations were low (22 microM) and did not increase over time. The concentration of GCV detected from the crystalline HDP-P-GCV in the core vitreous was 19.69 +/- 3.84 microM (n = 3) at day 1 and 1537.36 +/- 177.14 microM (n = 3) at day 7. The concentration of GCV released from crystalline HDP-P-GCV in peripheral vitreous was 32.86 +/- 5.07 microM (n = 3) at day 1 and 1805.78 +/- 327.94 microM (n = 3) at day 7. Detectable GCV concentration from both core and peripheral vitreous samples increased over time, however, the magnitude of GCV release from peripheral vitreous samples was higher (P < 0.05, t Test). CONCLUSION: In vitreous, HDP-P-GCV as a crystalline formulation was converted to GCV more rapidly than liposomal formulation of HDP-P-GCV. Vitreous cells may play an important role in the metabolism of either formulation of HDP-P-GCV delivered into vitreous.

Animals↗

Recurrent Kawasaki disease-like syndrome in a patient with acquired immunodeficiency syndrome.

A review of Kawasaki disease (KD)-like syndromes (KDLS) in patients with human immunodeficiency virus (HIV) raised the question whether vasculitis in children and KDLS in immunocompromised adults might be etiologically related. We describe a 42-year-old white man with AIDS and Kaposi sarcoma who presented with KDLS, which was diagnosed on the basis of clinical criteria for KD. Analysis of a conjunctival tissue sample revealed endothelial cell damage with fibrin deposition and infiltration of immunoglobulin A-secreting plasma cells.

AIDS-Related Opportunistic Infections↗

An orthotopic model for human uveal melanoma in SCID mice.

The microcirculation of primary uveal melanomas, their precursors, and their metastases is distinctive. Medium-sized and even large primary uveal melanomas typically lack significant zones of necrosis, suggesting that either these tumors are relatively well perfused or they are capable of growth in a severely blood-deprived microenvironment. In addition to normal choroidal vessels that are incorporated into nevi and most primary uveal melanomas, aggressive primary and metastatic uveal melanomas tend to contain patterns of extracellular matrix that surround spheroidal or cylindrical packets of tumor cells. Some components of this branching, looping, and interconnected system of matrix may be perfused. It is now known that the generation of this patterning is a characteristic of genetically dysregulated melanoma cells (nonaggressive tumor cells do not form these patterns and melanomas lacking branching, looping, or interconnected matrix patterns tend to follow a relatively indolent course). We developed an orthotopic model of an aggressive human uveal melanoma by injecting suspensions of the primary human choroidal melanoma cell line (OCM1) into the subretinal space of one eye of 20 SCID mice. All mice were examined daily for tumor growth and tumors developed in every eye within 3 weeks of injection. The tumors were characterized by extraocular extension and the development of looping matrix patterns characteristic of those seen in aggressive human uveal melanoma. As in human uveal melanomas, these patterns were perfused by blood in areas. The orthotopic injection of human uveal melanoma cells into the SCID mouse eye generates a model reproducing the matrix-associated microcirculatory patterns of aggressive primary human uveal melanomas. This model can be used to explore the molecular pathogenesis and modulation of this novel circulation in vivo, to facilitate our understanding of the blood flow to these tumors providing insight into perfusion and drug delivery, to enable testing of pharmacologic modulation of pattern formation and intratumoral blood flow, and to refine noninvasive methods such as confocal scanning laser ophthalmoscopy to detect the presence of these patterns by which ophthalmologists might assess the biological behavior of tumors as noninvasive substitute for biopsy.

Animals↗

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration.

PURPOSE: To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment. DESIGN: Randomized controlled clinical trial. METHODS: Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes. RESULTS: Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes. CONCLUSIONS: Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.

Aged↗

Effects of preoperative and postoperative epiretinal membranes on macular hole closure and visual restoration.

OBJECTIVE: To investigate the effects of epiretinal membranes (ERMs) on macular hole surgical results and postoperative visual restoration. DESIGN: A subgroup analysis arising from a multicenter, controlled, randomized clinical trial. PARTICIPANTS: Ninety-one phakic eyes with an idiopathic macular hole that underwent standard vitrectomy for macular hole repair with or without ERM peeling. METHODS: Preoperative, intraoperative, and postoperative data of macular status, ERM status, and visual function status were recorded, and their relationships were analyzed. MAIN OUTCOME MEASURES: Visual acuity and clinical features of macular hole and ERM on baseline examination and scheduled follow-ups. RESULTS: ERM peeling was associated with greater anatomic hole closure success rates (67% of the ERM peeled vs. 35% of nonpeeled, P = 0.03) but not associated with visual improvement in eyes with anatomic hole closure (2.9 lines improvement vs. 3.6 lines improvement, P > 0.5). Macular hole reopening was associated with excessive ERM growth (P = 0.005). Postoperative ERMs were more common in the eyes that underwent cataract surgery after vitrectomy (77% in aphakic and 36% in phakic eyes, P = 0.02). Macular hole edge approximation or hole appearance after initial vitrectomy for hole repair was stable over the average 18-month period in 89% of the eyes; only approximately 10% of the eyes underwent changes in their hole appearance. The hole edge approximation or hole appearance was associated with preoperative hole size and postoperative visual acuity. Preoperative hole size was found to be the major predictor of postoperative visual acuity (P < 0.005). CONCLUSIONS: Surgical ERM peeling increases the anatomic hole closure rate. The presence of postoperative ERMs was not associated with postoperative visual acuity; however, excessive ERM growth contributed to hole reopening. Preoperative hole size was the most sensitive predictor for postoperative visual acuity. Surgical intervention during the early stages of macular hole before ERM formation is strongly recommended.

Epiretinal Membrane↗

Complex microcirculation patterns detected by confocal indocyanine green angiography predict time to growth of small choroidal melanocytic tumors: MuSIC Report II.

PURPOSE: Multiple independent laboratories have confirmed the histologic observation that some tumor microcirculation patterns (MCPs) in uveal melanomas are associated strongly with death resulting from metastatic disease. Because these patterns are imageable with confocal indocyanine green angiography (ICG), we designed a prospective study to evaluate whether these angiographically detectable MCPs predict time to tumor growth. DESIGN: Observational case series, prospective, non-randomized. PARTICIPANTS: Ninety-eight patients with unilateral, small, choroidal melanocytic tumors. METHODS: The following information and tumor characteristics were recorded for each patient: demographic parameters, best-corrected visual acuity, intraocular pressure, related visual symptoms, location and dimension of tumor, pigmentation, orange pigment, drusen, tumor-associated hemorrhage, subretinal fluid, and confocal ICG angiographically determined microcirculation patterns-silent (avascularity), normal (preexisting normal choroidal vessels within the tumor), straight vessels, parallel without and with cross-linking, arcs without and with branching, loops, and networks. MAIN OUTCOME MEASURES: Time to growth of the tumor, with growth defined as an increase in the maximal apical tumor height of 0.5 mm measured by standardized A-scan ultrasonography, photographic documentation of an increase of the largest basal diameter of at least 1.5 mm, advancement of one tumor border of at least 0.75 mm, or a combination thereof. RESULTS: Twenty-eight of the 98 tumors in this study (29%) met the predetermined criteria for tumor growth. The median time to growth was 127 days (range, 51-625 days). The following tumor characteristics were significantly associated with time to tumor growth: flashes (P = 0.0224), orange pigment (P = 0.012), subretinal fluid (P < 0.001), maximum basal tumor diameter at initial examination (P = 0.015), maximum apical tumor height (P < 0.001), parallel with cross-linking MCP (P < 0.001), arcs with branching MCP (P = 0.006), loops (P < 0.001), and networks (P < 0.001). Of these, the angiographic documentation of any of the complex MCPs (parallel with cross-linking, arcs with branching, loops, networks, or a combination thereof) showed the strongest association with the time to tumor growth in a Cox proportional hazard model. CONCLUSIONS: The characteristics of our patient cohort are comparable by clinical and echographic parameters with cohorts for predicting tumor growth, described previously in the literature. In addition, we detected a novel clinical predictor of tumor growth: the confocal ICG angiographic detection of complex MCPs.

Adult↗