Capillary Refill-The Key to Assessing Dermal Capillary Capacity and Pathology in Optical Coherence Tomography Angiography.

BACKGROUND/OBJECTIVES: Standard optical coherence tomography angiography (OCTA) has been limited to imaging blood vessels actively undergoing perfusion, providing a temporary picture of surface microvasculature. Capillary perfusion in the skin is dynamic and changes in response to the surrounding tissue's respiratory, nutritional, and thermoregulatory needs. Hence, OCTA often represents a given perfusion state without depicting the actual extent of the vascular network. Here we present a method for obtaining a more accurate anatomic representation of the surface capillary network in human skin using OCTA, along with proposing a new parameter, the Relative Capillary Capacity (RCC), a quantifiable proxy for assessing capillary dilation potential and permeability. METHODS: OCTA images were captured at baseline and after compression of the skin. Baseline images display ambient capillary perfusion, while images taken upon capillary refill display the network of existing capillaries at full capacity. An optimization-based automated vessel segmentation method was used to automatically analyze and compare OCTA image sequences obtained from two volunteers. RCC was then compared with visual impressions of capillary viability. RESULTS: Our OCTA imaging sequence provides a method for mapping cutaneous capillary networks independent of ambient perfusion. Differences between baseline and refill images clearly demonstrate the shortcomings of standard OCTA imaging and produce the RCC biometric as a quantifiable proxy for assessing capillary dilation potential and permeability. CONCLUSION: Future dermatological OCTA diagnostic studies should implement the Capillary Refill Methods over standard imaging techniques and further explore the relevance of RCC to differential diagnosis and dermatopathology. Lasers Surg. Med. © The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

[Optical coherence tomography: from retina imaging to intraoperative use - a review]. / Ubersicht der apparativen Entwicklungen in der optischen Kohärenztomografie: von der Darstellung der Retina zur Unterstützung therapeutischer Eingriffe.

BACKGROUND: Optical coherence tomography (OCT) is new diagnostic procedure that has rapidly evolved in the last years. The recently developed spectral domain OCT allows one to increase the imaging speed by a hundred times compared to the first generation time domain OCT and enables three-dimensional imaging as well as real-time imaging of fast moving structures. Volumetric imaging improves the quantitative measurement of morphology and the evaluation of temporal changes. In addition, an exact correlation with images acquired with other imaging modalities is possible. Real-time imaging enables also the use of OCT during examinations with the slit-lamp and during ophthalmological surgery. METHODS: A spectral domain OCT was adapted to a slit lamp. 70 patients (91 eyes) were examined at the anterior or posterior segment of the eye. Images of healthy structures and different pathologies were compared to OCT images obtained with Stratus 3, Spectralis, and the SL-OCT. To demonstrate the feasibility of OCT during surgery, spectral domain OCT devices working with 20,000 and 210,000 A scans per second were coupled by specially developed optics to the camera port of a surgical microscope. The device was tested with phantoms and enucleated pig eyes. RESULTS AND CONCLUSIONS: A 5 kHz spectral domain OCT can image the retina during slit lamp-based indirect ophthalmoscopy with a quality similar to that of the Stratus 3. In addition, relevant structures of the anterior segment were imaged. Here, compared to commercially available devices, the imaged field was smaller and the angle of the anterior chamber was not directly visible due to the 830 nm wavelength, which had to be used for retinal imaging. Through the surgical microscope, a volumetric imaging of epithelium, Bowman's, Descemet's membranes, limbus, iris, lens, conjunctiva and sclera was demonstrated with several tens of centimetre working distance. Instruments and incisions in the cornea were visualised with 20 microm precision. Real-time imaging and visualisation of volumetric OCT data were also demonstrated. In principle, all technical problems of an intraoperative use of OCT have been solved and a clinical trial will start in the near future. OCT has the potential to improve the precision of surgical interventions and may even enable new interventions.

[Selective retina therapy in central serous chorioretinopathy with detachment of the pigmentary epithelium]. / Selektive Retina-Therapie bei Retinopathia centralis serosa mit Pigmentepithelabhebung.

BACKGROUND: Selective Retina Therapy (SRT) is a new and innovative laser treatment modality that selectively treats the retinal pigmentary epithelium while sparing the photoreceptors. This therapeutic concept appears to be particularly suitable for treating patients with acute or chronic central serous chorioretinopathy (CSC). We present preliminary results obtained in five patients who had CSC associated with pigmentary epithelium detachment (PED) and serous subretinal fluid (SRF) and who were treated with SRT. METHODS: This case series was made up of five male patients (mean age 47 years) with chronic CSC and SRF resulting from PED. Examinations performed before and at 1 month and 3 months after the treatment were: BCVA, FLA, OCT (Zeiss OCT III). For SRT, confluent treatment of the PED (area of leakage) was carried out using a pulsed frequency-doubled, Q-switched Nd-YLF prototype laser (lambda=527 nm, t= 1.7 s, 100 Hz, energy = 150-250 J). RESULTS: Best corrected visual acuity at baseline was 0.53, while after 4 weeks it was 0.56 and after 12 weeks, 0.5. At baseline leakage was seen at the PED on fluorescein angiography in all patients. After 4 weeks leakage activity was no longer noted on angiography in 4 of 5 patients. OCT at baseline showed SRF at the edge of the PED in all patients, but in 4 of the 5 patients this was no longer detectable after 4 weeks. CONCLUSION: SRT is a safe and effective treatment for patients with CSC in which PED has caused SRF. Not a single case of rip syndrome was observed in this study, even though the PED was treated confluently. Since SRT spares the photoreceptors it is particularly suitable for the treatment of CSC, especially when the origin of leakage is located close to the fovea. The results indicate that SRT leads to reconstruction of the outer blood-retina barrier.

[Selective retina therapy in patients with diabetic maculopathy]. / Selektive Retina-Therapie bei Patienten mit diabetischer Makulopathie.

Selective Retina Therapy (SRT) is a new laser treatment that selectively targets the retinal pigmen epithelium (RPE). In this study, we treated 39 patients presenting with nonischemic, focal and focal-diffuse diabetic maculopathy with SRT. In the main. the results indicate that SRT had stabilizing effects on visual acuity, angiographic leakage, lipid exudation, and foveal retinal thickness. SRT is safe and is especially useful for treating pathologies that are located close to the fovea, which cannot be treated with conventional argon laser photocoagulation.

[Selective retina therapy: methods, technique, and online dosimetry]. / Selektive Retinatherapie: Methodik, Technik und Online-Dosimetrie.

Selective retina therapy (SRT) is currently under evaluation, as a new and very subtle laser method, for the treatment of retinal disorders associated with a degradation of the retinal pigmentary epithelium (RPE). SRT makes it possible to selectively effect the RPE, sparing the adjacent neural retina with the photoreceptors and also the choroid below the RPE. In the best case, the therapy leads to regeneration of the RPE and a long-term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with complete thermal necrosis of and around the treated site, absolutely no scotoma occurs in SRT. This paper reviews the methods and mechanisms behind the selective effects of the RPE. In vitro and preclinical results are used to describe the bandwidth of selective effects with respect to different irradiation settings. An optoacoustic technique is introduced to visualize effects that cannot be seen by ophthalmoscopy and to facilitate dosimetry control without recourse to angiography completes the report.

Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results.

Selective retina therapy (SRT) is a new laser procedure for retinal diseases that are thought to be associated with a degradation of the retinal pigment epithelium (RPE). The aim of the irradiation is to selectively damage the RPE without affecting the neural retina, the photoreceptors and the choroid. Goal of the treatment is to stimulate RPE cell migration and proliferation into the irradiated areas in order to improve the metabolism at the diseased retinal sites. In a pilot study more than 150 patients with soft drusen, retinopathia centralis serosa (RCS) and macular edema were treated. The first 3-center international trial targets diabetic macular edema and branch vein occlusion. In this review, selective RPE effects are motivated and two modalities to achieve selective RPE effects will be introduced: a pulsed and a continuous wave scanning mode. The mechanism behind selective RPE-effects will be discussed reviewing in vitro results and temperature calculations. So far clinical SRT is performed by applying trains of 30 laser pulses from a Nd:YLF-Laser (527 nm, 1.7 micros, 100 Hz) to the diseased fundus areas. In the range of 450-800 mJ/cm(2) per pulse, RPE-defects in patients were proved angiographically by fluorescein or ICG-leakage. The selectivity with respect to surrounding highly sensitive tissue and the safety range of the treatment will be reviewed. With the laser parameters used neither bleeding nor scotoma, proved by microperimetry, were observed thus demonstrating no adverse effects to the choroid and the photoreceptors, respectively. During and after irradiation, it shows that the irradiated locations are ophthalmoscopically invisible, since the effects are very limited and confined to the RPE, thus a dosimetry control is demanded. We report on a non-invasive opto-acoustic on-line technique to monitor successful RPE-irradiation and compare the data to those achieved with standard angiography one-hour post treatment.

Topographic angiography and optical coherence tomography: a correlation of imaging characteristics.

PURPOSE: Topographic angiography (TAG) using confocal scanning laser angiography and optical coherence tomography (OCT) are new imaging modalities that have been introduced during recent years. OCT and TAG imaging were compared to specify the characteristics of each imaging modality. METHODS: TAG using fluorescein angiography (FA) provides a three-dimensional profile of the vascular structures based on the analysis of a set of 32 confocal images over a depth of 4 mm. OCT provides cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex (RPE-CC). The authors compared and evaluated both modalities in 10 patients with predominantly classic choroidal neovascularization (CNV), 10 patients with serous pigment epithelial detachment (PED), and 10 patients with geographic RPE atrophy, all secondary to age-related macular degeneration (ARMD). RESULTS: In patients with classic CNV, TAG detected neovascular structures and delineated their configuration. In PEDs pooling of extravascular fluid is demonstrated, and in geographic RPE atrophy TAG showed reduced choroidal perfusion. Classic CNV was demonstrated by OCT as a hyperreflective band at the level of the RPE-CC, and PED showed a dome-shaped RPE detachment. In geographic RPE atrophy, OCT imaged loss of the RPE band and had an increased depth resolution. CONCLUSIONS: TAG and OCT are useful imaging modalities in the evaluation of ARMD cases. TAG visualizes the vascular configuration and dynamic perfusion and leakage changes. OCT is able to document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. Both modalities may provide further valuable insight into ARMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.

Intraocular photodisruption with picosecond and nanosecond laser pulses: tissue effects in cornea, lens, and retina.

PURPOSE: Nd:YAG laser photodisruption with nanosecond (ns) pulses in the millijoule range is an established tool for intraocular surgery. This study investigates tissue effects in cornea, lens, and retina to assess whether picosecond (ps) pulses with energies in the microjoule range can increase the surgical precision, reduce collateral damage, and allow applications requiring more localized tissue effects than can be achieved with ns pulses. METHODS: Both ps and ns Nd:YAG laser effects on Descemet's membrane, in the corneal stroma, in the lens, and at the retina were investigated in vitro in bovine and sheep eyes and in cataractous human lens nuclei. For each tissue, the optical breakdown threshold was determined. The morphology of the tissue effects and the damage range of the laser pulses were examined by light and scanning electron microscopy. The cavitation bubble dynamics during the formation of corneal intrastromal laser effects were documented by time-resolved photography. RESULTS: The optical breakdown threshold for ps pulses in clear cornea, lens, and vitreous is, on average, 12 times lower than that for ns pulses. In cataractous lens nuclei, it is lower by a factor of 7. Using ps pulses, Descemet's membrane could be dissected with fewer disruptive side effects than with ns pulses, whereby the damage range decreased by a factor of 3. The range for retinal damage was only 0.5 mm when 200 microJ ps pulses were focused into the vitreous. Picosecond pulses could be used for corneal intrastromal tissue evaporation without damaging the corneal epithelium or endothelium, when the pulses were applied in the anterior part of the stroma. The range for endothelial damage was 150 microns at 80 microJ pulse energy. Intrastromal corneal refractive surgery is compromised by the laser-induced cavitation effects. Tissue displacement during bubble expansion is more pronounced than tissue evaporation, and irregular bubble formation creates difficulties in producing predictable refractive changes. CONCLUSIONS: The use of ps pulses improves the precision of intraocular Nd:YAG laser surgery and diminishes unwanted disruptive side effects, thereby widening the field of potential applications. Promising fields for further studies are intrastromal corneal refractive surgery, cataract fragmentation, membrane cutting, and vitreolysis close to the retina.

Three-dimensional topographic angiography in chorioretinal vascular disease.

PURPOSE: To evaluate a new angiographic technique that offers three-dimensional imaging of chorioretinal vascular diseases. METHODS: Fluorescein (FA) and indocyanine green angiography (ICGA) were performed using a confocal scanning laser ophthalmoscope. Tomographic series with 32 images per set were taken over a depth of 4 mm at an image frequency of 20 Hz. An axial analysis was performed for each x/y position to determine the fluorescence distribution along the z-axis. The location of the onset of fluorescence at a defined threshold intensity was identified and a depth profile was generated. The overall results of fluorescence topography were displayed in a gray scale-coded image and three-dimensional relief. RESULTS: Topographic angiography delineated the choriocapillary surface covering the posterior pole with exposed larger retinal vessels. Superficial masking of fluorescence by hemorrhage or absorbing fluid did not preclude detection of underlying diseases. Choroidal neovascularization (CNV) appeared as a vascular formation with distinct configuration and prominence. Chorioretinal infiltrates exhibited perfusion defects with dye pooling. Retinal pigment epithelium detachments (PEDs) demonstrated dynamic filling mechanisms. Intraretinal extravasation in retinal vascular disease was detected within a well-demarcated area with prominent retinal thickening. CONCLUSIONS: Confocal topographic angiography allows high-resolution three-dimensional imaging of chorioretinal vascular and exudative diseases. Structural vascular changes (e.g., proliferation) are detected in respect to location and size. Dynamic processes (e.g., perfusion defects, extravasation, and barrier dysfunction) are clearly identified and may be quantified. Topographic angiography is a promising technique in the diagnosis, therapeutic evaluation, and pathophysiological evaluation of macular disease.

Laser sclerostomy by pulsed-dye laser and goniolens.

We describe an ab-interno laser sclerostomy procedure using the method termed dye-enhanced ablation with a slit-lamp delivery system and special goniolens such that only the laser light beam penetrates the anterior chamber. The procedure uses a microsecond-pulsed-dye laser emitting at 666 nm and iontophoresis of methylene blue dye (absorption of 668 nm) into the sclera at the limbus to enhance the absorption of the laser light. We compared the number of pulses needed to perforate excised human sclera at pulse durations of 1.5, 20, and 300 microseconds. Pulse durations of 1.5 and 20 microseconds required 20 pulses or fewer to perforate excised human sclera with pulse energies of 75 to 100 mJ. The ab-interno laser sclerostomy procedure was performed in 54 eyes of Dutch-belted rabbits with pulse durations of 1.5 or 20 microseconds and a 100- or 200-microns incident spot diameter delivered using a CGF goniolens. Full-thickness fistulas were successfully created at both pulse durations in approximately 80% of eyes treated. A range of three to 25 pulses was required to perforate sclera with slightly fewer pulses and lower pulse energies at 1.5 microseconds compared with 20 microseconds. There were no significant complications from the procedure. This technique could permit filtration surgery to be performed on an outpatient basis.

Response of the retinal pigment epithelium to selective photocoagulation.

Multiple short argon laser pulses can coagulate the retinal pigment epithelium selectively, while sparing the adjacent neural retina and choroid; in contrast, continuous-wave laser irradiation typically damages the neural retina and choroid. The healing response to selective photocoagulation of the retinal pigment epithelium was studied in rabbits during a period of 4 weeks. The lesions were never visible ophthalmoscopically. During the healing period, the epithelium was reformed by a single sheet of hypertrophic retinal pigment epithelial cells. In contrast to continuous-wave photocoagulation, only minimal inflammatory response was found. Retinal pigment epithelial cells showed clear signs of viability, eg, phagocytized outer segments. The local edema in the photoreceptor layer and subretinal space found in the early stage disappeared when the blood-retinal barrier was reestablished. The choriocapillaris remained unaffected. No subsequent damage to the photoreceptors was found. This type of photocoagulation may be useful for retinal pigment epithelium-related diseases, eg, diffuse diabetic macular edema.

Retinal sparing by selective retinal pigment epithelial photocoagulation.

OBJECTIVE: To investigate whether photocoagulation of the retinal pigment epithelium is possible with sparing of the photoreceptors. METHODS: Mild laser effects of a neodymium:yttrium-lithium-fluoride (Nd:YLF) laser (527 nm) were applied to 17 patients. To establish the necessary energy, test exposures were performed to the lower macula (laser variables: 1.7 microseconds, 100 and 500 pulses applied in a train at 500 Hz, 20-130 microJ, 160 microm). Of 179 test lesions, 73 were followed up at various time intervals up to 1 year by performing microperimetry directly on top of the laser lesions. RESULTS: All of the test lesions were at the threshold of retinal pigment epithelial disruption, and none of the laser effects were visible by ophthalmoscopy during photocoagulation; they were detectable only by fluorescein angiography. After exposure with 500 pulses, retinal defects were detected in up to 73% of the patients (100 microJ) after the first day. Most of these defects were no longer detectable after 3 months. After exposure with 100 pulses, no defects could be detected with 70 and 100 microJ after 1 day. The absence of microscotomas in the follow-up period suggests that retinal damage was minimal or, if it occurred, was functionally repaired. CONCLUSION: By choosing proper energy and number of pulses, it is possible to produce retinal pigment epithelial effects with no subsequent retinal damage detectable by microperimetry.

Corneal ablation by nanosecond, picosecond, and femtosecond lasers at 532 and 625 nm.

We produced corneal excisions with nanosecond (ns)-, picosecond-, and femtosecond (fs)-pulsed lasers at visible wavelengths. The threshold energy for ablation was proportional to the square root of the pulse duration and varied from 2.5 microjoules (microJ) at 100 fs to 500 microJ at 8 ns. Excisions made with picosecond and femtosecond lasers was ultrastructurally superior to those made with nanosecond lasers and, at pulse energies near threshold, showed almost as little tissue damage as excisions made with excimer lasers at 193 nm. We conclude that ultrashort-pulsed lasers at visible and near-infrared wavelengths are a possible alternative to excimer lasers for corneal surgery and might have advantages over conventional ophthalmic neodymium-YAG lasers for some intraocular applications.

A comparison of retinal morphology viewed by optical coherence tomography and by light microscopy.

OBJECTIVE: To compare the cross-sectional images of primate retinal morphology obtained by optical coherence tomography (OCT) with light microscopy to determine the retinal components represented in OCT images. METHODS: Laser pulses were delivered to the retina to create small marker lesions in a Macaca mulatta. These lesions were used to align in vivo OCT scans and ex vivum histologic cross sections for image comparison. RESULTS: The OCT images demonstrated reproducible patterns of retinal morphology that corresponded to the location of retinal layers seen on light microscopic overlays. Layers of relative high reflectivity corresponded to horizontally aligned retinal components such as the nerve fiber layer and plexiform layers, as well as to the retinal pigment epithelium and choroid. In contrast, the nuclear layers and the photoreceptor inner and outer segments demonstrated relative low reflectivity by OCT. CONCLUSIONS: Retinal morphology and macular OCT imaging correlate well, with alignment of areas of high and low reflectivity to specific retinal and choroidal elements. Resolution of retinal structures by OCT depends on the contrast in relative reflectivity of adjacent structures. Use of this tool will enable expanded study of retinal morphology, both normal and pathologic, as it evolves in vivo.

A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes.

OBJECTIVE: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. DESIGN: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. PARTICIPANTS: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. RESULTS: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. CONCLUSIONS: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD.

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.

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study.

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.

Nd:YAG laser photodisruption of hemorrhagic detachment of the internal limiting membrane.

We used a Q-switched Nd:YAG laser to create an opening in the internal limiting membrane in three eyes with hemorrhagic detachment of the internal limiting membrane. In all instances, after membranotomy blood was rapidly cleared from the preretinal space resulting in prompt improvement in visual acuity. No retinal injury was observed. Nd:YAG laser photodisruption may be useful in the treatment of some cases of subinternal limiting hemorrhages.

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.

Argon laser retinal lesions evaluated in vivo by optical coherence tomography.

PURPOSE: To assess the in vivo evolution of argon laser retinal lesions by correlating the cross-sectional structure from sequential optical coherence tomography with histopathologic sectioning. METHODS: Argon laser lesions were created in the retinas of Macaca mulatta and evaluated by cross-section optical coherence tomography, which was compared at selected time points with corresponding histopathology. RESULTS: Argon laser lesions induced an optical coherence tomography pattern of early outer retinal relative high reflectivity with subsequent surrounding relative low reflectivity that correlated well with histopathologic findings. The in vivo optical coherence tomography images of macular laser lesions clearly demonstrated differences in pathologic response by retinal layer over time. CONCLUSION: The novel sequential imaging of rapidly evolving macular lesions with optical coherence tomography provides new insight into the patterns of acute tissue response by cross-sectional layer. This sequential imaging technique will aid in our understanding of the rapid evolution of retinal pathology and response to treatment in the research and clinical setting.