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David N Zacks

Publications and source records attributed to David N Zacks.

15 recordsLinked to original sources
PubMed2006

Predictors of visual outcome and choroidal neovascular membrane formation after traumatic choroidal rupture.

OBJECTIVE: To determine predictors of choroidal neovascularization (CNV) and visual outcome after traumatic choroidal rupture. METHODS: A retrospective review of patients with traumatic choroidal rupture diagnosed in the Retina Service, Massachusetts Eye and Ear Infirmary, Boston, between January 1993 and August 2001 was performed. Parametric and nonparametric statistical methods were used to evaluate visual prognosis, CNV, and retinal detachment after traumatic choroidal rupture. RESULTS: One hundred eleven cases were identified and reviewed. Visual acuity (VA) changes were recorded in all of the cases. Thirty-eight (34%) of the 111 patients recovered driving vision (VA > or =20/40). Rupture location was recorded in 107 cases. Recovery of driving vision was seen in 20 (59%) of 34 eyes with peripheral choroidal ruptures, 17 (22%) of 73 eyes with macular choroidal ruptures, 38 (38%) of 99 eyes without CNV, 1 (8%) of 12 eyes with CNV, 38 (40%) of 96 eyes without retinal detachment, and 1 (7%) of 15 eyes with retinal detachment. Older age and location of rupture within the arcades were positively associated with CNV formation (P = .04 and .03, respectively). Foveal location of rupture, multiple ruptures, and poor baseline VA were associated with failure to recover driving vision in univariate regression analyses. In multivariate analysis, rupture location and baseline VA were independently associated with visual outcome. Of 12 patients diagnosed with CNV, 5 were not treated, 4 were treated with argon laser photocoagulation, 1 was treated with surgery, 1 was treated with argon laser photocoagulation followed by surgery, and 1 was treated with verteporfin photodynamic therapy. CONCLUSIONS: Most patients with traumatic choroidal rupture do not achieve final VA of 20/40 or better. Poor visual outcome was most highly associated with a macular rupture and baseline VA of less than 20/40. The formation of CNV was most strongly associated with older age and macular choroidal rupture.

Adolescent↗
PubMed2006

Activation of signaling pathways and stress-response genes in an experimental model of retinal detachment.

PURPOSE: Despite the high metabolic demands of the neural retina, its detachment from the retinal pigment epithelium does not lead to immediate death for most of the cells. This study was undertaken to test the hypothesis that intrinsic protective mechanisms are activated in the neural retina during early stages of retinal detachment. METHODS: Retinal detachments were created in Brown Norway rats by injection of 1% hyaluronic acid into the subretinal space. Gene expression profiles of retinas detached for 24 hours were generated with a gene microarray (rat U34 GeneChips; Affymetrix, Santa Clara, CA) and compared to the profiles from control attached retinas in a robust multiarray protocol and false-discovery-rate analysis. Changes in individual, differentially expressed genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Additional qRT-PCR and immunoblot analyses were performed for additional selected genes. RESULTS: Genome-wide expression profiling revealed 27 genes that are differentially expressed in retinas detached for 24 hours. In silico analysis and functional clustering suggested that most genes belonged to three signaling pathways: interleukin-6/STAT, transforming growth factor-beta/Smad, and aryl hydrocarbon receptor oxidative stress response. Additional analyses of selected genes from these pathways demonstrated a time-dependent increase in their expression in detached retinas. CONCLUSIONS: Retinal detachment results in the early activation of stress-response genes and specific signaling pathways. This adaptive response may enable the photoreceptor cells to survive the acute phase of a retinal detachment, and it is the breakdown of these protective mechanisms in chronic disease that leads to the ultimate death of the cell.

Animals↗
PubMed2005

Effect of intravitreal triamcinolone acetonide on susceptibility to experimental bacterial endophthalmitis and subsequent response to treatment.

OBJECTIVES: Recent reports of high endophthalmitis rates after intravitreal triamcinolone acetonide injection have raised concerns about the safety of this treatment. We sought to evaluate the effect of intravitreal triamcinolone injection on (1) the susceptibility to experimental bacterial endophthalmitis and (2) the subsequent therapeutic response to antibiotic treatment. DESIGN: For the susceptibility study, the right eye of 40 New Zealand white rabbits received an intravitreal injection of a known quantity of Staphylococcus epidermidis organisms. Half of the eyes received a simultaneous intravitreal injection of triamcinolone acetonide, 4 mg. All eyes were examined daily for signs of endophthalmitis (photophobia, conjunctival injection, and vitritis) using standardized grading protocols (scaled from 0 to 4 with increasing severity). On day 7, vitreous cultures were obtained. For the therapeutic response study, the right eye of 12 rabbits received an intravitreal injection of S epidermidis organisms sensitive to vancomycin. Half of the eyes received a simultaneous intravitreal injection of triamcinolone acetonide, 4 mg. All 12 eyes received an intravitreal injection of vancomycin hydrochloride, 1 mg, on development of the first signs of endophthalmitis. All eyes were examined daily for 7 additional days. On day 7 after treatment, vitreous cultures were obtained. RESULTS: In the susceptibility study, all 40 eyes developed signs of endophthalmitis. In eyes that received intravitreal bacteria plus triamcinolone, 17 (85%) of the 20 vitreous cultures were positive, whereas only 6 (30%) were positive in the 20 eyes receiving bacteria alone (P = .001). The vitritis was significantly increased in the bacteria plus triamcinolone group compared with the bacteria-only group (17 of 20 vs 7 of 20 with 4+ vitritis, respectively; P = .003). In the therapeutic response study, all 12 eyes developed clinical signs of endophthalmitis within 48 hours. All vitreous samples obtained 7 days after intravitreal vancomycin injection were culture negative. However, the severity of vitritis at the time of vitreous sampling was less in the eyes receiving triamcinolone plus bacteria compared with eyes receiving bacteria alone (0 of 6 vs 5 of 6 with 4+ vitritis, respectively; P = .02). CONCLUSIONS: In eyes with experimentally induced bacterial endophthalmitis, the presence of intravitreal triamcinolone results in a higher culture-positive rate and a higher degree of inflammation, suggesting an impaired ocular immune response and greater susceptibility to infection. However, in eyes with experimentally induced bacterial endophthalmitis receiving early treatment with intravitreal antibiotics, triamcinolone appears to suppress the ocular inflammatory response without impairing the therapeutic effect. CLINICAL RELEVANCE: These data suggest that caution must be exercised when combining intravitreal triamcinolone injection with intraocular surgery.

Animals↗
PubMed2005

Treatment of metastatic tumors of the choroid with proton beam irradiation.

OBJECTIVE: To describe the clinical outcomes of patients treated by proton beam irradiation for choroidal metastatic tumors. DESIGN: Noncomparative case series. PARTICIPANTS: A retrospective chart review was performed on a series of 63 patients (76 eyes) with choroidal metastases treated with proton beam therapy between December 1989 and September 2000. METHODS: Patients were treated with 2 fractions of 14 cobalt gray equivalents (CGEs) (CGE = proton Gy x relative biological effectiveness 1.1), each using a nonoperative "light-field" technique. Ophthalmologic follow-up was available for 46 patients (55 eyes), with a mean follow-up time of 10 months. The medical record or the Social Security Death Index was used to obtain survival status, which was available in 94% of cases. MAIN OUTCOME MEASURES: Tumor regression, recurrence, treatment-associated complications, and visual acuity were evaluated by ophthalmologic examination and ultrasonography. Eye retention and length of survival also were assessed. RESULTS: At the time of ocular diagnosis, 49 patients reported a history of a primary cancer. Median survival time after ocular diagnosis was 16 months through May 2003. Most choroidal metastases were dome shaped (62%) and located at the posterior pole (95%). Mean tumor height was approximately 3.5 mm, and serous retinal detachment was seen in 63% of cases. Eighty-four percent of treated tumors regressed completely within 5 months of treatment, and none of these recurred. Retinal detachment resolved in 82% of patients within 3.8 months after treatment, and visual acuity was preserved or improved in 47% of the patients. Complications occurred in 56% of cases and included madarosis, keratitis, dry eye syndrome, cataract, neovascular glaucoma, chorioretinal atrophy, radiation papillopathy, and radiation maculopathy. None of the treated eyes required enucleation. CONCLUSIONS: Proton beam irradiation is a useful therapeutic approach for choroidal metastases; it allows retention of the globe, achieves a high probability of local tumor control, and helps to avoid pain and visual loss. Although complications occur in most cases, many of these are minor and are not associated with a change in function. This modality is accurate and efficient, because it only entails 2 treatment fractions and does not require surgery for tumor localization.

Adult↗
PubMed2005

Retinal and intracranial arteriovenous malformations: Wyburn-Mason syndrome.

A 7-year-old girl who failed a vision screening examination was found to have a retinal arteriovenous malformation (AVM) in her right eye along with a small angioma of her right lower lip. Magnetic resonance imaging and cerebral angiography revealed a large AVM involving the thalamus and basal ganglia as well as a small AVM involving the right ophthalmic artery. The combination of retinal and intracranial AVMs is known as Wyburn-Mason syndrome. The retinal AVMs of this syndrome do not grow or bleed. Visual loss is usually the result of optic neuropathy from associated orbitocranial AVMs. The natural course of the intracranial AVMs of this syndrome is poorly documented. However, they tend to be extensive and inaccessible and therefore difficult to treat.

Cerebral Angiography↗
PubMed2004

Hypopyon uveitis associated with systemic lupus erythematosus and antiphospholipid antibody syndrome.

PURPOSE: To report a case of hypopyon uveitis associated with systemic lupus erythematosus and antiphospholipid antibody syndrome. METHODS: Interventional case report: a 49-year-old woman with a history of systemic lupus erythematosus and antiphospholipid antibody syndrome presented with sudden onset of pain, redness, photophobia, and decreased vision in the left eye. Examination revealed hypopyon uveitis and vaso-occlusive retinopathy. RESULTS: Following treatment with intravenous steroids and cyclophosphamide, the patient's vision improved from CF to 20/80 with no inflammation 6 months following initial presentation. CONCLUSIONS: In this case, systemic lupus and antiphospholipid syndrome were associated with hypopyon uveitis. Prompt treatment with systemic immunosuppressive therapy resulted in improvement in the hypopyon uveitis and vaso-occlusive retinopathy.

Antiphospholipid Syndrome↗
PubMed2004

FAS-mediated apoptosis and its relation to intrinsic pathway activation in an experimental model of retinal detachment.

PURPOSE: To determine whether the FAS-mediated apoptosis pathway becomes activated in the retina after retinal detachment and to investigate the temporal relationship between the activation of the FAS-pathway and the intrinsic apoptosis pathway involving caspase-9 and cytochrome c. METHODS: Experimental retinal detachments were created in Brown-Norway rats by injecting 10% hyaluronic acid into the subretinal space. Retinal tissue was harvested at 2, 4, 8, 24, 72, and 168 hours after creation of the detachment. Immunoprecipitation was performed to assess for FAS-receptor/FAS-ligand complex formation, and activation of caspase-8 and BID (a member of the Bcl-2 family of proteins) was assessed by Western blot analysis. A caspase-9 activity assay and immunoprecipitation of the caspase-9/cytochrome c complex were performed at these same time points. Specific pathway inhibition was performed with the caspase-9 inhibitor zLEHD.fmk or neutralizing antibodies against either the FAS-receptor or FAS-ligand. Transcription levels of FAS and intrinsic pathway intermediates were assessed as a function of time after retinal detachment by using quantitative real-time polymerase chain reaction. RESULTS: Retinal detachment resulted in the time-dependent formation of the FAS-receptor/FAS-ligand complex that preceded the peak of caspase-9 activity and caspase-9/cytochrome c complex formation. Cleavage of caspase-8 and truncation of BID were also observed. Injection of zLEHD.fmk into the subretinal space of a detached retina resulted in decreased caspase-9 activity, as did injection of anti-FAS-receptor antibody into either the subretinal space or the vitreous. Retinal detachment resulted in the transcriptional upregulation of the FAS-receptor, FAS-ligand, caspase-8 and BID, but not caspase-9 and cytochrome c. CONCLUSIONS: The FAS-mediated apoptosis pathway becomes activated and transcriptionally upregulated after retinal detachment. The peak of FAS activation precedes that of the intrinsic pathway, and inhibition of FAS activation can decrease caspase-9 activity.

Animals↗
PubMed2003

Caspase activation in an experimental model of retinal detachment.

PURPOSE: To test for apoptotic photoreceptor cell death and caspase activation as a function of time after induction of an experimental retinal detachment. METHODS: Retinal detachments were created in Brown Norway rats by injecting 10% hyaluronic acid into the subretinal space using a transvitreous approach. Light microscopy and terminal dUTP-biotin nick end-labeling (TUNEL) was performed at 1, 3, 5, and 7 days after detachment to assess for the morphologic features associated with apoptosis. Western blot analysis of retinal protein extracts was performed using antibodies against caspase-3, -7, and -9 and poly-ADP ribose-polymerase (PARP) at 1, 3, and 5 days after detachment. RESULTS: Light microscopic analysis of detached retinas showed the presence of pyknotic nuclei in the outer nuclear layer and disruption of the normal organization of the photoreceptor outer segments. TUNEL-staining was positive in the outer nuclear layer only in the detached portions of the retina. Western blot analysis confirmed the time-dependent activation of caspase-3, -7, and -9 and PARP in the detached retinas. No morphologic stigmata of apoptosis or caspase activation was detected in attached retinas. CONCLUSIONS: The apoptotic photoreceptor cell death in experimental retinal detachments is associated with caspase activation.

Animals↗
PubMed2002

Electroretinograms as an indicator of disease activity in birdshot retinochoroidopathy.

PURPOSE: To determine whether electroretinogram results can help predict the success in tapering of immunosuppressive medication in patients with birdshot retinochoroidopathy. METHODS: Fifteen patients with birdshot retinochoroidopathy who had at least three serial electroretinograms (ERG) during the course of their disease were included in the study. Charts of patients seen at the Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts were retrospectively reviewed. Seven parameters of the ERGs were examined: dim scotopic amplitude, bright scotopic amplitude, bright scotopic implicit time, single-flash photopic amplitude, single-flash photopic implicit time, 30 Hz flicker amplitudes, and 30 Hz flicker implicit times. For each parameter the patients were divided into two groups, those with normal and those with abnormal responses at the time their immunosuppressive medication taper was initiated. The percentage of patients in each group who were able to successfully taper their immunosuppressive medication was calculated. A successful taper of medication was defined as no recurrence of disease signs or symptoms for at least 1 year after the medication was terminated. RESULTS: Abnormalities in the bright scotopic response amplitudes and 30 Hz flicker implicit times were associated with recurrence of inflammation as immunosuppressive therapy was tapered. CONCLUSION: ERG can serve as a useful adjunct in helping determine when to initiate tapering of immunosuppressive therapy in patients with birdshot retinochoroidopathy.

Adult↗
PubMed2002

Verteporfin photodynamic therapy in the rat model of choroidal neovascularization: angiographic and histologic characterization.

PURPOSE: To develop a model of verteporfin photodynamic therapy (PDT) for experimental choroidal neovascularization CNV in the rat. METHODS: A laser injury model was used to induce experimental CNV in rats. The transit and accumulation of the photosensitizer verteporfin was assessed angiographically in CNV lesions, to determine the optimal time for delivery of light energy. The CNV lesions were then treated with verteporfin PDT, with two doses of verteporfin (3.0 and 6.0 mg/m(2)) and four activating doses of light energy (10, 25, 50, and 100 J/cm(2)). Closure of the CNV was assessed both angiographically and histologically. Verteporfin PDT was also performed on areas of normal choroid and retina at the two verteporfin doses and four light energy doses. The effect of these treatments on these structures was also assessed angiographically and histologically. RESULTS: Peak verteporfin intensities in the CNV were detected at 15 to 20 minutes after intravenous injection. Rates of closure of the CNV varied as a function of the dose of verteporfin and of the activating light energy. Angiographic closure of the CNV correlated with damage to the neovascular complex, as seen with light and electron microscopy. Damage to areas of normal choroid and retina treated with verteporfin PDT also varied as a function of the verteporfin and light energy doses. CONCLUSIONS: Verteporfin PDT for experimental CNV in the rat is a feasible, effective, and reproducible model that can be used for testing the efficacy of adjunctive therapy to verteporfin PDT.

Animals↗
PubMedDate not supplied

Combined intravitreal injection of triamcinolone acetonide and panretinal photocoagulation for concomitant diabetic macular edema and proliferative diabetic retinopathy.

PURPOSE: To present our results of intravitreal injection of triamcinolone acetonide (IVTA) combined with panretinal photocoagulation (PRP) for patients with concomitant clinically significant diabetic macular edema and proliferative diabetic retinopathy. METHODS: Charts of patients undergoing combined IVTA and PRP were reviewed. Outcome measures included visual acuity, presence of macular edema, and response of proliferative disease to laser photocoagulation. RESULTS: Four patients were included in this study. All patients maintained stable visual acuity during the treatment period. All patients had improvement in the amount of macular edema, despite the application of PRP, as well as complete regression of their proliferative disease. There were no short-term complications associated with IVTA or PRP. CONCLUSION: Combination treatment with IVTA and PRP may provide benefit in patients with diffuse diabetic macular edema who require urgent PRP for proliferative diabetic retinopathy by preventing exacerbation of macular edema.

Adult↗