Macular Degeneration: Ciulla TA

Ciulla TA. · No affiliation provided · Acta Ophthalmol Scand. · Pubmed #12752045 No free full text.

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Ciulla TA. · No affiliation provided · Br J Ophthalmol. · Pubmed #11316702 links to  free full text

This publication has no abstract.

Ciulla TA, Rosenfeld PJ. · Vitreoretinal Service, Midwest Eye Institute, Indianapolis, Indiana 46280, USA. · Curr Opin Ophthalmol. · Pubmed #19417570 No free full text.

Abstract: PURPOSE OF REVIEW: The most important recent advance in the treatment of neovascular age-related macular degeneration (AMD) is the development of antivascular endothelial growth factor (anti-VEGF) therapeutic agents that preserve and improve visual acuity by arresting choroidal neovascular growth and reducing vascular permeability. This review describes the current literature on the use of this therapeutic approach in the management of neovascular AMD. RECENT FINDINGS: Two anti-VEGF agents, pegaptanib sodium and ranibizumab, are currently approved by the United States Food and Drug Administration for the treatment of neovascular AMD. In addition, off-label use of a third anti-VEGF agent, bevacizumab, as a treatment option for neovascular AMD has become common worldwide. Other anti-VEGF agent strategies that have shown efficacy include small interfering RNA agents to silence the VEGF gene and receptor and the fusion protein VEGF trap. SUMMARY: The accumulation of preclinical and clinical evidence implicating VEGF-A in the pathogenesis of neovascular AMD has provided a strong rationale for the development of anti-VEGF agents for this disease. Anti-VEGF therapies have been used successfully in the clinic, encouraging their use in the treatment of other neovascular eye diseases.

Ciulla TA, Rosenfeld PJ. · Vitreoretinal Service, Midwest Eye Institute, Indianapolis, Indiana 46280, USA. · Curr Opin Ophthalmol. · Pubmed #19381089 No free full text.

Abstract: PURPOSE OF REVIEW: Anti-vascular endothelial growth factor (anti-VEGF) therapies that arrest choroidal angiogenesis and reduce vascular permeability have revolutionized clinical practices for neovascular eye diseases. This review describes anti-VEGF strategies that are being evaluated in ocular diseases, other than neovascular age-related macular degeneration, in which neovascularization plays a critical role in pathogenesis. RECENT FINDINGS: Early studies of the anti-VEGF agents, pegaptanib sodium, ranibizumab, bevacizumab, VEGF trap, and bevasiranib in the treatment of various neovascular diseases (e.g., diabetic macular edema, retinal vein occlusion, choroidal neovascularization) have shown promising results. The efficacy and safety of these agents, either alone or combined with standard treatments (e.g., laser photocoagulation), anti-inflammatory agents, or other non-VEGF-based antiangiogenic therapies, is actively investigated. Non-VEGF-driven pathways and growth factors other than VEGF may play important roles in pathogenesis and are included in certain combination therapies with VEGF inhibitors. SUMMARY: The discovery of VEGF-A's role in the pathogenesis of neovascular ocular disease provided a strong rationale for the development of anti-VEGF-based therapies. There is now ample evidence that anti-VEGF therapies are viable treatment options for these diseases. Nevertheless, large, randomized controlled trials are still awaited to confirm early safety and efficacy findings from small, open-label prospective studies.

Ehrlich R, Harris A, Kheradiya NS, Winston DM, Ciulla TA, Wirostko B. · Indiana University School of Medicine, Department of Ophthalmology, Indianapolis, IN 46202, USA. · Clin Interv Aging. · Pubmed #18982917 links to  free full text

Abstract: Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch's membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly.

Davidson JA, Ciulla TA, McGill JB, Kles KA, Anderson PW. · Division of Endocrinology, University of Texas, Southwestern Medical School, Dallas, Texas 75230, USA. · Endocrine. · Pubmed #17992608 No free full text.

Abstract: The objective is to review the most common causes of vision loss in patients with diabetes with the goal of better managing patients with diabetic eye disease. In this review, the causes of vision loss, and the clinical evaluation and management of diabetic retinopathy (DR) and diabetic macular edema (DME) are outlined. Patients with diabetes mellitus have an increased risk of vision loss and blindness. In patients with diabetes, the primary mechanism responsible for vision loss is centrally involved DME or clinically significant macular edema (CSME), defined as vascular leakage resulting in fluid accumulation that affects the center of the macula. DR and DME are thought to result from the effects of excessive blood glucose on the vessels that produces microvascular damage. The progression of DR can be slowed by intensive glycemic and blood pressure control. Severe visual loss from proliferative DR and moderate visual loss from DME can be reduced by laser photocoagulation. DR and DME are diagnosed on dilated retinal examination and confirmed with diagnostic testing. Many experts and associations recommend that patients with diabetes have an yearly, thorough, dilated eye exam. This manuscript describes the case history of a patient with diabetes and vision loss.

Comer GM, Ciulla TA, Heier JS, Criswell MH. · Indiana University School of Medicine, Department of Ophthalmology, 702 Rotary Circle, Indianapolis, IN 46202, USA. · Expert Opin Emerg Drugs. · Pubmed #15757408 No free full text.

Abstract: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the industrialised world. Within the past decade, researchers have introduced many promising prevention and treatment options in an attempt to minimise the central vision loss imparted from AMD. Based on large-scale, randomised, prospective, placebo-controlled trials, a specially formulated combination of the antioxidants vitamin C, vitamin E, beta-carotene, copper and zinc is the only proven means of AMD prophylaxis. Thermal laser photocoagulation and photodynamic therapy with verteporfin are the only standard treatment options. However, efficacy is limited and treatment is only applicable to a minority of AMD patients. Thus, alternative pharmacological interventions are in all phases of clinical development. Researchers are guardedly optimistic that these advances may change the entire approach to AMD management in the near future. This review article will detail the currently accepted treatment options, as well as describe several of the more promising investigational pharmacological approaches to AMD.

Comer GM, Ciulla TA, Criswell MH, Tolentino M. · Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Drugs Aging. · Pubmed #15631528 No free full text.

Abstract: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the industrialised world. Although relatively simple to diagnose through direct visualisation augmented with rapid sequence fluorescein angiography, treatment has presented a far greater challenge because the true aetiology of AMD is largely unknown. Within the past decade, researchers have introduced many new, potentially promising treatment and prevention options in an attempt to minimise the damage imparted from AMD. They capitalise on many of the theoretical and known factors contributing to AMD progression. A high-dose of an orally administered combination of the antioxidants ascorbic acid (vitamin C), tocopherol (vitamin E) and beta-carotene, in addition to copper and zinc, is the only widely accepted preventive therapy. Thermal laser photocoagulation and verteporfin photodynamic therapy are the only standard treatment options available based on large scale, randomised, prospective, placebo-controlled trials; however, efficacy is limited and only a minority of patients who present with AMD are eligible for these treatments. Many other preventive and treatment options are in all phases of clinical studies and expected to change the entire approach to AMD management in the near future. For example, alternative antioxidants, drusen ablation, apheresis and HMG-CoA reductase inhibitors have shown promise in some studies by preventing or slowing the progression of certain forms of AMD. In addition, alternative photodynamic therapies, low-intensity laser, antiangiogenic medications, radiation treatment and surgery have demonstrated the ability, albeit to differing degrees, to inhibit or possibly even reverse the severe vision loss often associated with AMD characterised by choroidal neovascularisation.

Ciulla TA, Walker JD, Fong DS, Criswell MH. · Midwest Eye Institute, 201 Pennsylvania Parkway, Indianapolis, IN 46280, USA. · Curr Opin Ophthalmol. · Pubmed #15118508 No free full text.

Abstract: PURPOSE OF REVIEW: Corticosteroids are traditionally used for inflammatory disorders because of their ability to diminish neutrophil transmigration, limit access to sites of inflammation, and decrease cytokine production. More recently, however, investigators have focused on the angiostatic and antipermeability properties of corticosteroids for posterior segment diseases such as age-related macular degeneration (AMD), diabetic retinopathy, and macular edema. Both new angiostatic and traditional corticosteroids are currently undergoing evaluation as new delivery techniques such as intravitreal injection and intraocular sustained-release devices facilitate high local angiostatic and antipermeability concentrations while minimizing extraocular toxicity. The purpose of this review is to discuss recent work concerning both the mechanism and effectiveness of these newer treatments. RECENT FINDINGS: Steroids may exert a beneficial effect in AMD-related choroidal neovascular membranes (CNVM) through inhibition of CNVM-promoting macrophages and direct inhibition of angiogenic growth factors. They may also alter extracellular matrix turnover and inhibit matrix metalloproteinases involved in CNVM formation. Intravitreal steroid injections potently inhibit experimental CNVM in primates and rats and have shown promise in some early human pilot trials. In proliferative diabetic retinopathy, steroids may directly inhibit growth factors such as vascular endothelial derived growth factor and inhibit leukocytes that play an important role in early microvascular alterations. Intravitreal steroid injections inhibit experimental preretinal neovascularization in pigs and rats, and rubeosis in some early human studies. In addition, the effect of steroids on vascular permeability has led to their use for macular edema from many causes such as diabetes and venous occlusive disease. SUMMARY: The use of steroids to treat a number of retinal diseases is gaining wide spread acceptance. The apparent short-term success must be balanced by the fact that the long-term safety and efficacy have yet to be determined for any of these approaches. A number of large randomized prospective clinical trials of steroid compounds and new delivery systems are currently under way for AMD, diabetic retinopathy, uveitis, and other retinovascular diseases, and hopefully these studies will provide guidance about the use of these new modalities.

Ciulla TA, Amador AG, Zinman B. · Midwest Eye Institute, Indianapolis, Indiana, USA. · Diabetes Care. · Pubmed #12941734 links to  free full text

Abstract: Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of blindness in the working-age population of most developed countries. The increasing number of individuals with diabetes worldwide suggests that DR and DME will continue to be major contributors to vision loss and associated functional impairment for years to come. Early detection of retinopathy in individuals with diabetes is critical in preventing visual loss, but current methods of screening fail to identify a sizable number of high-risk patients. The control of diabetes-associated metabolic abnormalities (i.e., hyperglycemia, hyperlipidemia, and hypertension) is also important in preserving visual function because these conditions have been identified as risk factors for both the development and progression of DR/DME. The currently available interventions for DR/DME, laser photocoagulation and vitrectomy, only target advanced stages of disease. Several biochemical mechanisms, including protein kinase C-beta activation, increased vascular endothelial growth factor production, oxidative stress, and accumulation of intracellular sorbitol and advanced glycosylation end products, may contribute to the vascular disruptions that characterize DR/DME. The inhibition of these pathways holds the promise of intervention for DR at earlier non-sight-threatening stages. To implement new therapies effectively, more individuals will need to be screened for DR/DME at earlier stages-a process requiring both improved technology and interdisciplinary cooperation among physicians caring for patients with diabetes.

Rechtman E, Ciulla TA, Criswell MH, Pollack A, Harris A. · Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, 46202, USA. · Expert Opin Pharmacother. · Pubmed #12083992 No free full text.

Abstract: Age-related macular degeneration (AMD) is the leading cause of irreversible loss of central vision in people aged > 50 years in the western world. Until recently, the only proven treatment to reduce the risk of vision loss from its more severe neovascular form was laser photocoagulation, but this treatment was suitable for only 15% of cases. Photodynamic therapy (PDT) with verteporfin was recently proposed to be effective in reducing the risk of visual loss for an estimated 20 - 30% of neovascular AMD patients. This review covers AMD epidemiology, the mechanism of PDT, the 2-year results of the two major clinical studies of PDT with verteporfin, the cost-effectiveness of PDT and the current research status of other drugs for PDT in AMD.

Ciulla TA, Piper HC, Xiao M, Wheat LJ. · Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46260, USA. · Curr Opin Ophthalmol. · Pubmed #11734684 No free full text.

Abstract: Presumed ocular histoplasmosis involves the classic triad of discrete atrophic choroidal scars in the macula or midperiphery known as histo spots, peripapillary atrophy, and choroidal neovascularization, which leads to severe loss of central vision. The histo spots from which the choroidal neovascularization develop do not show active inflammation but do represent focal defects in Bruch membrane that could facilitate development of choroidal neovascularization. The macular photocoagulation studies unequivocally show the benefit of photocoagulation compared with observation in reducing the risk of vision loss in patients with presumed ocular histoplasmosis, well defined extrafoveal or juxtafoveal choroidal neovascularization, and choroidal neovascularization in the peripapillary area. However, laser treatment itself causes an absolute scotoma correlating with the site of the laser photocoagulation scar, and subfoveal choroidal neovascularization is not amenable to laser photocoagulation because this would cause a blinding central scotoma. Consequently, other treatments have been sought. The Verteporfin in Ocular Histoplasmosis study evaluated photodynamic therapy for subfoveal choroidal neovascularization caused by presumed ocular histoplasmosis and demonstrated stabilization of the choroidal neovascularization and visual acuity benefit. In addition to photodynamic therapy, antiangiogenic compounds are being developed for choroidal neovascularization caused by age-related macular degeneration, and these agents will likely be of benefit in presumed ocular histoplasmosis associated choroidal neovascularization. Finally, submacular surgery for the removal of subfoveal choroidal neovascularization has promising results. The results of these research efforts will produce more effective therapeutic approaches in the future.

Ciulla TA, Harris A, Martin BJ. · Indiana University School of Medicine, Indianapolis, Indiana, USA. · Acta Ophthalmol Scand. · Pubmed #11284745 No free full text.

Abstract: PURPOSE: To review the role of ocular perfusion in the pathophysiology of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the industrialized world. METHODS: Medline search of the literature published in English or with English abstracts from 1966 to 2000 was performed using various combinations of relevant key words. RESULTS: Vascular defects have been identified in both nonexudative and exudative AMD patients using fluorescein angiographic methods, laser Doppler flowmetry, indocyanine green angiography, and color Doppler imaging. CONCLUSION: Although these studies lend some support to the vascular pathogenesis of AMD, it is not possible to determine if the choroidal perfusion abnormalities play a causative role in nonexudative AMD, if they are simply an association with another primary alteration, such as a primary RPE defect or a genetic defect at the photoreceptor level, or if they are more strongly associated with one particular form of this heterogeneous disease. Further study is warranted.

Harris A, Chung HS, Ciulla TA, Kagemann L. · Department of Ophthalmology, Indiana University, Indianapolis 46202, USA. · Prog Retin Eye Res. · Pubmed #10438154 No free full text.

Abstract: New technologies have facilitated the study of the ocular circulation. These modalities and analysis techniques facilitate very precise and comprehensive study of retinal, choroidal, and retrobulbar circulations. These techniques include: 1. Vessel caliber assessment; 2. Scanning laser ophthalmoscopic fluorescein angiography and indocyanine green angiography to image and evaluate the retinal circulation and choroidal circulation respectively; 3. Laser Doppler flowmetry and confocal scanning laser Doppler flowmetry to measure blood flow in the optic nerve head and retinal capillary beds; 4. Ocular pulse measurement; and 5. color Doppler imaging to measure blood flow velocities in the central retinal artery, the ciliary arteries and the ophthalmic artery. These technique have greatly enhanced the ability to quantify ocular perfusion defects in many disorders, including glaucoma and age-related macular degeneration, two of the most prevalent causes of blindness in the industrialized world. Recently it has become clear, in animal models of glaucoma, that retinal ganglion cells die via apoptosis. The factors that initiate apoptosis in these cells remain obscure, but ischemia may play a central role. Patients with either primary open-angle glaucoma or normal-tension glaucoma experience various ocular blood flow deficits. With regard to age-related macular degeneration, the etiology remains unknown although some theories include primary retinal pigment epithelial senescence, genetic defects such as those found in the ABCR gene which is also defective in Stargardt's disease and ocular perfusion abnormalities. As the choriocapillaris supplies the metabolic needs of the retinal pigment epithelium and the outer retina, perfusion defect in the choriocapillaris could account for some of the physiologic and pathologic changes in AMD. Vascular defects have been identified in both nonexudative and exudative AMD patients using new technologies. This paper is a comprehensive update describing modalities available for the measurement of all new ocular blood flow in human and the clinical use.

Heier JS, Boyer DS, Ciulla TA, Ferrone PJ, Jumper JM, Gentile RC, Kotlovker D, Chung CY, Kim RY, Anonymous00353. · Ophthalmic Consultants of Boston, Boston, MA 02114, USA. · Arch Ophthalmol. · Pubmed #17101999 links to  free full text

Abstract: OBJECTIVE: To investigate the safety and efficacy of intravitreal ranibizumab treatment combined with verteporfin photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization secondary to age-related macular degeneration. METHODS: In this 2-year, phase I/II, multicenter, randomized, single-masked, controlled study, patients received monthly ranibizumab (0.5 mg) (n = 106) or sham (n = 56) injections. The PDT was performed 7 days before initial ranibizumab or sham treatment and then quarterly as needed. MAIN OUTCOMES MEASURES: Proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months (primary efficacy outcome) and the incidence and severity of adverse events. RESULTS: At 12 months, 90.5% of the ranibizumab-treated patients and 67.9% of the control patients had lost fewer than 15 letters (P<.001). The most frequent ranibizumab-associated serious ocular adverse events were intraocular inflammation (11.4%) and endophthalmitis (1.9%; 4.8% if including presumed cases). On average, patients with serious inflammation had better visual acuity outcomes at 12 months than did controls. Key serious nonocular adverse events included myocardial infarctions in the PDT-alone group (3.6%) and cerebrovascular accidents in the ranibizumab-treated group (3.8%). CONCLUSION/APPLICATION TO CLINICAL PRACTICE: Ranibizumab + PDT was more efficacious than PDT alone for treating neovascular age-related macular degeneration. Although ranibizumab treatment increased the risk of serious intraocular inflammation, affected patients, on average, still experienced visual acuity benefit.

Heier JS, Antoszyk AN, Pavan PR, Leff SR, Rosenfeld PJ, Ciulla TA, Dreyer RF, Gentile RC, Sy JP, Hantsbarger G, Shams N. · Ophthalmic Consultants of Boston, Boston, Massachusetts 02114, USA. · Ophthalmology. · Pubmed #16483659 No free full text.

Abstract: OBJECTIVE: To assess safety of repeated intravitreal injections of ranibizumab in treating neovascular age-related macular degeneration (AMD), and to assess changes in visual acuity (VA) and AMD lesion characteristics. DESIGN: Multicenter, controlled, open-label, clinical trial. PARTICIPANTS: Sixty-four patients with subfoveal predominantly or minimally classic AMD-related choroidal neovascularization. METHODS: In part 1, subjects were randomized to monthly intravitreal ranibizumab for 3 months (4 injections of 0.3 mg or 1 injection of 0.3 mg followed by 3 injections of 0.5 mg; n = 53) or usual care (UC; n = 11). In part 2, subjects could continue their regimen for 3 additional months or cross over to the alternative treatment. MAIN OUTCOME MEASURES: Adverse events (AEs), intraocular pressure (IOP), VA, and lesion characteristics assessed by fluorescein angiography and fundus photography. RESULTS: Of the 64 randomized subjects, 62 completed the 6-month study. Twenty of 25 subjects (80%) randomized to 0.3 mg, and 22 of 28 subjects (79%) randomized to 0.5-mg ranibizumab in part 1 continued on that treatment in part 2; 9 of 11 (82%) subjects randomized to UC in part 1 crossed over to ranibizumab treatment in part 2. The most common AEs with ranibizumab were reversible inflammation and minor injection-site hemorrhages. Serious AEs were iridocyclitis, endophthalmitis, and central retinal vein occlusion (1 subject each). Postinjection, IOP increased transiently in 22.6% of ranibizumab-treated eyes in parts 1 and 2. After 4 ranibizumab injections (day 98), mean (+/- standard deviation) VA had increased 9.4+/-13.3 and 9.1+/-17.2 letters in the 0.3- and 0.5-mg groups, respectively, but had decreased 5.1+/-9.6 letters with UC. In part 2 (day 210), VA increased from baseline 12.8+/-14.7 and 15.0+/-14.2 letters in subjects continuing on 0.3 and 0.5 mg, respectively. Visual acuity improved from baseline > or =15 letters in 26% (day 98) and 45% (day 210) of subjects initially randomized to and continuing on ranibizumab, respectively, and areas of leakage and subretinal fluid decreased. No UC subject had a > or =15-letter improvement at day 98. CONCLUSIONS: Repeated intravitreal injections of ranibizumab had a good safety profile and were associated with improved VA and decreased leakage from choroidal neovascularization in subjects with neovascular AMD.

Harris A, Ciulla TA, Pratt LM, Rechtman E, Kagemann L, Piper HC, Garzozi HJ. · Department of Ophthalmology, Indiana University School of Medicine, IN 46260, USA. · Br J Ophthalmol. · Pubmed #12770975 links to  free full text

Abstract: AIM: To comprehensively evaluate the effects of dorzolamide on the choroidal and retinal circulation in patients with age related macular degeneration (AMD). METHODS: In this randomised, double masked, parallel study, 36 non-exudative AMD patients were randomised in a 2 to 1 fashion to placebo versus topical dorzolamide and underwent assessment of their choroidal and retinal circulation. Scanning laser ophthalmoscope indocyanine green angiograms (ICGA) were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary region were evaluated by plotting intensity of fluorescence of each area over time. The means of the choroidal filling times and the heterogeneity of the filling times were assessed. Scanning laser ophthalmoscope fluorescein angiography (FA) was evaluated for retinal arteriovenous passage (AVP) times by plotting intensity of fluorescence of retinal vessels over time. Assessment was performed at baseline and at 4 months. RESULTS: Compared to placebo, AMD patients treated with dorzolamide showed a significantly increased rapidity of choroidal filling in the superior and inferior peripapillary regions (p=0.007, p=0.02, respectively). No significant difference in choroidal filling times was found in any of the perifoveal areas (p=0.9). Also, on FA assessment, treatment with dorzolamide showed no statistical differences in AVP times (p=0.19). CONCLUSIONS: Dorzolamide may increase peripapillary choroidal perfusion in non-exudative AMD patients. Further studies are merited.

Ciulla TA, Danis RP, Klein SB, Malinovsky VE, Soni PS, Pratt LM, Pugh NO, Morphis JG, Bloch C, Cameron J. · Retina Service, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Am J Ophthalmol. · Pubmed #12470761 No free full text.

Abstract: PURPOSE: To examine the effect of proton beam irradiation on subfoveal choroidal neovascular membranes (CNVM) associated with age-related macular degeneration (AMD).Randomized, prospective, sham-controlled, double-masked treatment trial. METHODS: Thirty-seven subjects with subfoveal CNVM due to AMD were randomly assigned to 16-Gy proton irradiation delivered in two fractions 24 hours apart or to sham control treatment. Recruitment was halted at 37 subjects for ethical reasons regarding randomization to sham treatment when Food and Drug Administration approval of Visudyne was anticipated. RESULTS: Proton irradiation was associated with a trend toward stabilization of visual acuity, but this association did not reach statistical significance. No correlations were found within the fluorescein angiography data, including greatest linear dimension of CNVM total size, area of active leakage, area of associated subretinal hemorrhage, and intensity. CONCLUSIONS: With the acceptance of photodynamic therapy, future studies will require more complex design and larger sample size to determine whether radiation can play either a primary or adjunctive role in treating these lesions.

Danis RP, Ciulla TA, Pratt LM, Anliker W. · Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, USA. · Retina. · Pubmed #10872928 No free full text.

Abstract: PURPOSE: To examine the effects of intravitreal injection of 4.0 mg triamcinolone acetonide on the visual and clinical course of exudative age-related macular degeneration. METHODS: A randomized clinical trial of a single injection of triamcinolone acetonide into the vitreous cavity of experimental eyes at baseline versus observation of untreated subjects was performed in 27 patients followed up for 6 months. Inclusion criteria included exudative age-related macular degeneration with subfoveal or occult choroidal neovascularization, and visual acuity between 20/40 and 20/400. Examination, acuity assessment, fundus photography, and fluorescein angiography were performed at baseline and at 3 and 6 months after enrollment. LogMAR visual acuity was compared between groups by a repeated measures analysis of variance model. Masked assessment of photographic studies was performed and groups were compared with Fisher's exact test. RESULTS: Visual acuity was significantly better in the treated group compared with control subjects at 3 and 6 months (P < 0.005). Fundus photography and angiography were more likely to show stability or improvement at 3 and 6 months in the treated group (P = 0.05). Intraocular pressure elevation was seen in 25% of treated patients, but was controlled with topical medications. Progression of cataract was more frequently seen in the treated group. CONCLUSIONS: Intravitreal triamcinolone acetonide may provide short-term improvement in visual acuity and fundus findings in exudative macular degeneration. These findings must be considered preliminary and should be followed by multicenter, masked, placebo-controlled trials with long-term follow-up.

Rechtman E, Harris A, Siesky B, Kagemann L, Danis RP, Sines D, Ciulla TA. · Goldschleger Eye Institute, Tel-Hashomer, Israel. · Ophthalmic Surg Lasers Imaging. · Pubmed #17552388 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: To evaluate the relationship between retrobulbar and choroidal hemodynamics in non-neovascular age-related macular degeneration. PATIENTS AND METHODS: Thirteen patients with age-related macular degeneration were assessed by both color Doppler imaging and scanning laser ophthalmoscope indocyanine green (ICG) angiography. Color Doppler imaging was used to measure peak systolic and end diastolic velocity (from which the resistance index, a measure of the resistance to flow downstream, was calculated) in the retrobulbar vessels. Scanning laser ophthalmoscope ICG angiograms were analyzed by area dilution analysis for quantitative choroidal fluorescence intensity assessment. Color Doppler imaging parameters were correlated with scanning laser ophthalmoscope ICG area dilution analysis parameters. RESULTS: A good correlation was found between the posterior ciliary arteries resistance index and scanning laser ophthalmoscope ICG area dilution analysis fluorescence duration. CONCLUSIONS: Scanning laser ophthalmoscope ICG area dilution analysis "duration" may serve as an alternative to color Doppler imaging in assessing the resistance to blood flow in the posterior ciliary arteries.

Hu W, Criswell MH, Ottlecz A, Cornell TL, Danis RP, Lambrou GN, Ciulla TA. · Retina Service Research Laboratories, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Retina. · Pubmed #16340537 No free full text.

Abstract: PURPOSE: To determine whether lumiracoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that exhibits anti-inflammatory and antiangiogenic properties, can inhibit experimental choroidal neovascular membrane (CNVM) development induced by focal laser trauma in a well-characterized Brown Norway rat CNVM model. METHODS: Over a 35-day period, 24 rats received daily oral gavage dosages of 20 mg/kg lumiracoxib in a 0.5% (w/v) suspension of sodium carboxymethylcellulose (CMC), while a control group received the 0.5% CMC suspension only. After 7 days, eight laser photocoagulation sites were placed concentrically around the optic disk to induce CNVMs. Thirty-five days later, fundus photography and fluorescein angiography (FA) were performed and eyes were processed for histopathologic analysis. RESULTS: Masked FA grading of lesion sites revealed a small, but statistically significant difference (P<0.0001) in late stage staining intensity and leakage between the mean group scores of treated (1.4) and control (1.7) eyes. Histopathologic analysis demonstrated that the mean CNVM thickness +/- SD of 38 +/-19 microm (n=24 eyes, 175 photocoagulation sites) in the lumiracoxib-treated animals was reduced by 30% (P<0.001) compared to the CNVM mean thickness+/- SD of 54+/- 20 microm (n=24 eyes, 171 photocoagulation sites) in the control animals. CONCLUSION: Systemic administration of the selective COX-2 inhibitor lumiracoxib results in a partial but significant reduction in CNVM development in the rat laser-trauma model and thus may be clinically beneficial as a potential inhibitor of CNVM formation in exudative age-related macular degeneration.

Criswell MH, Ciulla TA, Lowseth LA, Small W, Danis RP, Carson DL. · Retina Service Research Laboratories, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, 46260, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15914638 links to  free full text

Abstract: PURPOSE: Anastomotic vessels in exudative age-related macular degeneration (AMD) represent a serious clinical feature that reportedly does not respond well to either photocoagulation or photodynamic therapy (PDT). Anastomoses also occur in various animal models of choroidal neovascularization (CNV). In the present study, anastomotic vessels and their patency were evaluated in two primate CNV laser-trauma models after PDT, by using two novel photosensitizers. METHODS: In cynomolgus (Macaca fascicularis) and squirrel (Saimiri sciureus) monkey eyes (n = 20), matrix placement of laser photocoagulation sites elicited CNV as a component of the development of fibrovascular tissue (FVT). FVT sites received PDT according to specific drug infusion and laser light treatment parameters. FVTs and anastomoses were evaluated by fundus photography, fluorescein angiography, and histologic examination. RESULTS: Anastomoses averaged approximately 48% of FVT sites, with greatest occurrence in the macaque. Although PDT with each photosensitizer effectively produced FVT closure, both retinal vessels and anastomoses remained patent. CONCLUSIONS: Although PDT is effective in closing the choroidal neovascularization in FVT, this technique was ineffective in occluding anastomotic vessels and their associated tributaries within the mid- to proximal retina. Various factors (vascular diameter, composition, blood flow, orientation) may contribute to continued anastomotic patency. By convention, such vessels would typically be defined as chorioretinal anastomoses (CRAs); however, continuing studies suggest the possibility that these neovessels constitute dual-origin hybrids. Regardless of origin, viable anastomoses provide one potential mechanism for revascularization to occur after PDT and may help to explain why CRAs are considered a poor prognostic sign in patients with AMD.

Ciulla TA, Hammond BR. · Retina Service, Midwest Eye Institute, Methodist Medical Plaza North, Indianapolis, Indiana 46280, USA. <> · Am J Ophthalmol. · Pubmed #15488784 No free full text.

Abstract: PURPOSE: Increasing evidence has linked retinal lutein and zeaxanthin (termed macular pigment, MP) to the risk of age-related macular degeneration (AMD). Currently, however, studies differ regarding the question of whether MP declines with age or age has an effect in patient populations being assessed. This study assessed MP across the lifespan with an emphasis on assessing MP in a cross-section of elderly including those with lenticular or age-related macular degeneration, or both. DESIGN: Prospective, observational, cross-sectional study. METHODS: SETTING: Institution. STUDY POPULATION: Cross-sectional study of normal, cataractous, and AMD subjects tested in Indianapolis, Indiana, including 390 subjects, 22 with cataracts and 59 with age-related macular degeneration. OBSERVATIONAL PROCEDURE: MP density was measured with a one-degree diameter test field at 460 nm using a psychophysical method based on heterochromatic flicker photometry. MAIN OUTCOME MEASURES: MP optical density. RESULTS: MP does not appear to change as a function of age (r = +.04) when examining subjects across the lifespan (from 18-88 years). There was a slight tendency (slope = -.0027, r = -.11) for MP to decline when only the elderly subjects were considered, but this trend was not significant (P < .12) for any of the groups considered (normal, cataractous, or AMD). CONCLUSIONS: MP does not change significantly with age, even when elderly subjects with cataracts and AMD are considered. Using heterochromic flicker photometry, elderly subjects display a full range of MP density that is similar to young subjects.

Ciulla TA, Criswell MH, Danis RP, Fronheiser M, Yuan P, Cox TA, Csaky KG, Robinson MR. · Retina Service Research Laboratories, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA. · Br J Ophthalmol. · Pubmed #12881350 links to  free full text

Abstract: AIM: To determine if intravitreal microimplants containing triamcinolone acetonide (TAAC) inhibit experimental fibrovascular proliferation (FVP) induced by laser trauma in a rat as a model of choroidal neovascular membranes (CNVMs). METHODS: 20 anaesthetised male Brown Norway rats received a series of eight krypton red laser lesions per eye (647 nm, 0.05 s, 50 micro m, 150 mW). Three types of sterilised TAAC microimplant designs were evaluated: implant A consisting of 8.62% TAAC/20% polyvinyl alcohol (PVA) matrix (by dry weight); implant B consisting of 3.62% TAAC/20% PVA matrix; and implant C consisting of a dual 8.62% TAAC/20% PVA matrix design combined with a central core (0.5 mm) of compressed TAAC to extend the implant release time. For each animal studied, one eye received one of the three aforementioned TAAC implant designs, while the fellow eye received a control implant consisting of PVA but without TAAC. The animals were sacrificed at day 35 and ocular tissues were processed for histological analysis. Serial histological specimens were methodically assessed in a masked fashion to analyse each laser lesion for the presence or absence of FVP; maximum FVP thickness for each lesion was measured from the choriocapillaris. RESULTS: All three types of TAAC implants inhibited FVP relative to controls in a statistically significant fashion. In the eyes that received implant A (n = 8), the mean thickness of the recovered lesions (n = 36) measured 32 (SD 22) micro m, compared to 52 (30) micro m (p <0.005) for the recovered lesions (n = 40) from the fellow control eyes. In the eyes that received implant B (n = 6), the mean thickness of the recovered lesions (n = 31) measured 28 (15) micro m, compared to 50 (29) micro m (p <0.001) for the lesions (n = 19) recovered from the fellow control eyes. In the eyes that received implant C (n = 6), the mean thickness of the recovered lesions (n = 21) measured 39 (24) micro m, compared to 65 (30) micro m (p <0.001) for the lesions (n = 39) recovered from the fellow control eyes. CONCLUSIONS: All three of the tested TAAC microimplant designs produced potent inhibition of FVP in a rat model of CNVMs. There were no differences in inhibition of FVP between the three different types of implants evaluated. This study provides evidence that: (1) corroborates previous investigations that propose TAAC as a potential treatment for CNVMs in humans, and (2) demonstrates TAAC can be effectively delivered via long acting sustained release intraocular microimplants. It should be noted, however, that the FVP observed in this rat laser trauma may not reflect the CNVM observed in human with exudative age related macular degeneration (AMD).

Ranson NT, Danis RP, Ciulla TA, Pratt L. · Department of Ophthalmology, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA. · Br J Ophthalmol. · Pubmed #11973247 links to  free full text

Abstract: BACKGROUND: Laser treatment of extrafoveal well delineated choroidal neovascularisation in exudative age related macular degeneration has a high rate of failure with subsequent severe vision loss from subfoveal involvement. Laser treatment may limit scotoma size, but is unpalatable because of early persistent vision loss. Intravitreal triamacinolone injection may be an acceptable alternative therapy in such disparate cases. METHODS: 14 consecutive patients with recurrent neovascularisation were treated with a single 4.0 mg injection of triamacinolone and followed for up to 1 year. Visual results were compared with published data from the Macular Photocoagulation Study of recurrent neovascularisation. RESULTS: Mean visual acuity remained stable at about 20/200 throughout the study period in the treated patients. This is comparable to the outcomes in the Macular Photocoagulation Study for laser retreated patients, and better than the observation group. CONCLUSIONS: Intravitreal triamcinolone may be an acceptable treatment of subfoveal recurrent neovascularisation while avoiding early persistent vision loss from laser retreatment.