Horst Laqua

Photodynamic Therapy With Verteporfin for Choroidal Neovascularization Caused by Age-related Macular Degeneration: Results of a Single Treatment in a Phase 1 and 2 Study

OBJECTIVE To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. DESIGN Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. SETTING Four ophthalmic centers in North America and Europe providing retinal care. PARTICIPANTS Patients with subfoveal CNV caused by age-related macular degeneration. METHODS Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. RESULTS The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5), -1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm2) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150 J/cm2. Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a significantly better visual acuity outcome (+0.8 line) than eyes in which CNV leakage progressed (-0.8 line). CONCLUSIONS Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm2, no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified.

Long-term results of vitrectomy and silicone oil in 500 cases of complicated retinal detachments

We retrospectively analyzed by life table analysis the visual and functional results in 500 eyes that underwent combined vitrectomy and silicone oil for various types of complicated retinal detachments. The cumulative proportion of eyes with attached retina was 77% at six months postoperatively, with a range of 71% for perforating injuries to 85% for posterior holes. The proportion of eyes with a visual acuity of 5/200 or better was 69% at six months, with a range of 56% for perforating injuries to 81% for posterior holes. Sixty-nine eyes had poor visual function despite an attached retina, primarily because of cataract (18 eyes) and preexisting retinal or optic disease (31 eyes). Visual function in eyes with clear optical media and an attached retina was stable over time, except in patients with diabetes. No clinical evidence of retinal toxicity to silicone oil was noted.

Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples

Abstract · Background: Conventional photocoagulation of subfoveal choroidal neovascularization (CNV) is often accompanied by visual loss due to thermal damage to adjacent retinal structures. Photodynamic therapy (PDT) allows vascular occlusion by selective photochemical destruction of vascular endothelial cells only. In a pilot study we evaluated the use of PDT in CNV. · Methods: In a clinical phase I/II trial, patients with subfoveal CNV were treated with PDT. Benzoporphyrin derivative monoacid ring A (BPD) was used as sensitizer at a drug dose of 6 mg/m2 or 12 mg/m2. Irradiation was performed via a diode laser emitting at 690 nm coupled into a slit lamp. Safe and maximum tolerated light doses were defined by dose escalation from 25 to 150 J/cm2. Photodynamic effects were documented ophthalmoscopically and angiographically. · Results: Sixty-one patients received a single course of BPD-PDT. Preliminary results suggest no damage to retinal structures within the treated area clinically. Retinal perfusion was not altered, while CNV demonstrated immediate absence of fluorescein leakage in the majority of lesions subsequent to PDT. At optimized parameters (6 mg/m2 and 50 J/cm2) complete cessation of leakage from classic CNV occurred in 100% of cases at 1 week and in 50% at week 4. In 70–80% of classic CNV, leakage reappeared at week 12, but markedly less than before treatment. · Conclusion: PDT allows temporary absence of leakage from CNV with preservation of visual acuity. The long-term prognosis of CNV secondary to age-related macular degeneration treated with repeated courses of PDT is being evaluated in a phase III trial.

Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study

BACKGROUND Subthreshold (retinal pigment epithelium) photocoagulation is a new photocoagulation method, which treats the retinal pigment epithelium (RPE) and avoids damage to the neural retina. The initial results in this prospective pilot study on various macular diseases are presented. METHODS 12 patients with diabetic maculopathy (group I), 10 with soft drusen (group II), and four with central serous retinopathy (CSR) (group III) were treated and followed up for 1 year. Treatment was achieved using a train of repetitive short laser pulses (1.7 μs) of a green Nd:YLF laser (parameters: 527 nm, 100 and 500 pulses, repetition rate: 500 Hz, spot size: 160 μm, energies: 70–100 μJ). Laser energy was based on the visibility of test lesions on fluorescein angiography (50–130 μJ). Patients were examined at various times by ophthalmoscopy, fluorescein and ICG angiography, and infrared imaging. RESULTS After 6 months hard exudates disappeared in six out of nine patients in group I and leakage disappeared in six out of 12 diabetic patients. In group II drusen were less in seven out of 10 patients. In group III serous detachment disappeared in three out of four cases. Visual acuity was stable in all cases. None of the laser lesions was clinically visible immediately. After 1 day most lesions were visible as yellowish RPE depigmentation. After 3 months some of the lesions were visible as hyperpigmented areas but most were not. Fluorescein angiography showed leakage only in the first week. Infrared imaging showed that most lesions can be visualised in groups I and II after a period longer than 1 week as hyperreflective areas. CONCLUSION This study showed that subthreshold (RPE) photocoagulation is effective in some cases of diabetic maculopathy, drusens, and in CSR. Visibility of laser burns is not always necessary in the treatment of macular diseases presented here. Infrared imaging is an effective and non-invasive way of visualising subthreshold (RPE) laser burns.

Benefits and complications of photodynamic therapy of papillary capillary hemangiomas

OBJECTIVE To evaluate the potential benefit and risks of photodynamic therapy (PDT) in the treatment of papillary capillary hemangioma. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Five patients with solitary capillary hemangioma on the temporal portion of the optic nerve presenting with exudative decompensation and decrease in visual acuity (VA). METHODS All eyes received a standardized PDT treatment with 6 mg/kg body surface area verteporfin and application of 100 J/cm(2) light at 692 nm. One to three PDT courses were performed until resolution of exudation was achieved. A continuous follow-up was provided with documentation 1 week before and at 4 to 6 weeks, 3 months, and 12 months after the last treatment application. MAIN OUTCOME MEASURES Functional parameters included best-refracted VA (Early Treatment Diabetic Retinopathy Study), and central scanning laser ophthalmoscope (SLO) scotometry and peripheral (automated perimetry) visual fields; anatomic parameters were presence of retinal edema or serous detachment (ophthalmoscopy) and tumor size (ultrasonography). RESULTS Pretreatment VA levels ranged from 20/40 to 20/800; posttreatment levels ranged from 20/64 to 20/2000. Tumor regression with resolution of macular exudate and serous retinal detachment was obtained in all eyes. A decline in VA of 1, 3, and 10 lines, respectively, was documented in three patients. Complications included transient decompensation of vascular permeability, occlusion of retinal vessels, and ischemia of the optic nerve. CONCLUSIONS PDT is successful in reducing tumor size and exudative activity. Vaso-occlusive effects at the level of the retina and optic nerve compromise the functional benefit. Parameters proven safe in choroidal neovascularization may be inappropriate in retinal capillary lesions of the optic nerve.

Slit-lamp-adapted optical coherence tomography of the anterior segment

Abstract · Purpose: To evaluate the diagnostic potential of a slit-lamp-adapted optical coherence tomography (OCT) system as an in vivo imaging device for routine clinical examination of the anterior segment of the eye. · Patients and methods: In a pilot study, healthy volunteers and patients with different pathologies of the anterior segment were examined with a slit-lamp-adapted OCT system using 100–200 axial scans with 100-Hz line-scan frequency. The scan length is variable up to 7 mm, and the axial depth is 1.5 mm in tissue. · Results: The slit-lamp-adapted OCT system allowed direct biomicroscopic imaging of the measured area. Anatomic structures and morphological changes anterior to the attenuating iris pigment epithelium could be visualized with high accuracy. Biometric analyses of the cornea, the chamber angle, the iris and secondary cataract were possible. Complete demonstration of the chamber angle was difficult due to the backscattering properties of the anterior part of the sclera and the consequent shadowing of the most peripheral part of the iris. · Conclusions: Slit-lamp-adapted OCT is a useful diagnostic tool which allows in vivo microscopic cross-sectional imaging of the anterior segment and precise measurement of ocular structures.

Corneal Optical Coherence Tomography Before and Immediately After Excimer Laser Photorefractive Keratectomy

PURPOSE To investigate the representation of the corneal structure with optical coherence tomography before and immediately after excimer laser photorefractive keratectomy. METHODS Twenty-four eyes of 24 patients with myopia and myopic astigmatism were prospectively studied. The corneal thickness and the corneal profile were assessed with slit-lamp-adapted optical coherence tomography preoperatively and immediately after excimer laser photorefractive keratectomy. RESULTS The attempted mean spherical equivalent of the refractive corrections was -6.7 +/- 3.6 (mean +/- SD) diopters with a mean calculated stromal ablation depth of 91 +/- 38 microm. The corneal optical coherence tomography was reproducible in all patients, demonstrating a mean decrease of central corneal thickness after epithelial debridement and excimer laser photorefractive keratectomy of 118 +/- 45 microm. The comparison of the calculated stromal ablation depth and the corneal thickness changes determined by corneal optical coherence tomography revealed a significant linear relationship with a correlation coefficient of 0.88 (P <.001). The flattening of the corneal curvature was confirmed in all patients with the optical coherence tomography system and correlated with the attempted refractive correction (r =.82, P <.001). CONCLUSIONS The slit-lamp-adapted optical coherence tomography system presented in this study allowed noncontact, cross-sectional, and high-resolution imaging of the corneal configuration. This initial clinical evaluation demonstrated that corneal optical coherence tomography could be a promising diagnostic modality to monitor corneal changes of thickness and curvature before and after excimer laser photorefractive keratectomy.

Preparation of autologous platelets for the ophthalmologic treatment of macular holes.

BACKGROUND: Platelet concentrates were recently used for ophthalmologic treatment of macular holes. This strategy was investigated to define standardized blood bank components.

Photodynamic Therapy With Verteporfin for Choroidal Neovascularization Caused by Age-related Macular Degeneration

OBJECTIVES To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. DESIGN Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. SETTING Four ophthalmic centers in Europe and North America providing retinal care. METHODS Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. RESULTS The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications. CONCLUSIONS Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treatment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss.

Quality of salivary tears following autologous submandibular gland transplantation for severe dry eye.

Abstract · Background: This study aimed to characterise the composition of the pre-ocular fluid after transplantation of the autologous submandibular gland (SMG) for patients with severe dry eye. · Methods: Stimulated and unstimulated pre-ocular fluid from 15 patients (17 eyes) with a viable SMG graft (“SMG-salivary tears”), as well as normal tears and SMG saliva (20 normal subjects/ 20 eyes), was sampled. As global tear parameters, fern pattern analysis and SDS gel electrophoresis were performed. As specific quality parameters, total protein content, secretory immunoglobulin A (SIgA), lysozyme, amylase, sodium, potassium and osmolality were measured using routine laboratory methods. The flow rate of SMG-salivary tears was determined in 5 patients by means of sequential scintillography. · Results: The fern pattern of SMG-salivary tears was coarse and thus more similar to normal SMG saliva than tears. SDS gel electrophoresis of the SMG-salivary tears showed albumin and two unidentified proteins in addition to the normal tear pattern. Osmolality and total protein content of SMG-salivary tears were higher than in normal SMG saliva, but still lower than in normal tears. High activities of normal tear antibacterial proteins (SIgA, lysozyme and amylase) were detected in the salivary tears. Stimulation of the secretion did not alter the composition of SMG-salivary tears. The flow rate of SMG-salivary tears was closer to that of normal tears than normal SMG saliva. · Conclusion: Salivary tears resulting from SMG-transplantation represent condensed SMG saliva. Thus their quality is intermediate between normal tears and normal SMG saliva. High levels of secretory proteins demonstrate that the gland maintains an active function. Surgical denervation and residual tear components from the ocular surface are the most likely factors to cause the complex differences between normal SMG saliva and SMG-salivary tears. The effects of this secretion on the ocular surface are currently being evaluated in a clinical and laboratory study.