Occlusion Of Choriocapillaris Research Articles

Attenuation of irradiated choroid and its regional vortex veins in central serous chorioretinopathy after photodynamic therapy

We retrospectively studied 12 eyes of 12 patients with central serous chorioretinopathy (CSC) to investigate choroidal thickness changes following half-fluence photodynamic therapy (PDT) using widefield choroidal thickness maps obtained by optical coherence tomography (OCT). Additionally, we assessed the relationship between choroidal thickness changes and the regional vortex veins as visualized on widefield en face OCT of the choroid. Pre-treatment en face images of the choroidal vasculature were superimposed on subtracted choroidal thickness maps before and 3 months after half-fluence PDT. The choroidal thickness decreased mainly in the irradiated macular area and in the region of vortex veins which function as drainage for the macula in all eyes. Eleven eyes (91.7%) showed choroidal thinning in the nasal area which overlapped with the nasal vortex vein distribution. Moreover, in 10 (90.9%) of those eyes, we observed intervortex venous anastomosis across the vertical watershed zone. Quantitative analysis revealed that the reduction in choroidal thickness was most pronounced in the macular area. Furthermore, the choroidal thickness reduction in the area with macular drainage vortex veins was significantly greater than that in the area without such vortex veins. These results suggest that half-fluence PDT might decrease choroidal thickness due to choriocapillaris occlusion in the irradiated macula, possibly leading to diminished venous drainage from the macula to regional vortex veins. Moreover, venous blood flow through the anastomotic vessels from the macular drainage vortex veins into the nasal vortex veins might be reduced post-treatment.

A new Chlorin formulation promotes efficient photodynamic action in choriocapillaris of rabbit’s eyes

Age-related macular degeneration (AMD) as well as other choroidal diseases, demand novel therapeutic methods. Photodynamic therapy (PDT), which uses light and photosensitizer (PS) to cause specific vascular occlusion in the macula, is an interesting alternative. The only drug approved for the PDT treatment of AMD (Verteporfin) has a natural tendency to aggregate, demanding an expensive separation procedure during purification. We report a novel and affordable PS that is intrinsically protected against aggregation, the Monomeric Chlorin at High Concentration (MCHC-Chlorin), whose liposomal formulation was developed to provoke effective photodynamic action on the choroidal vasculature. Our report starts by stablishing the conditions to allow the efficient synthesis of MCHC-Chlorin in high yields (92%). We then tested the light stimulated occlusion of choriocapillary vessels in rabbit’s eyes induced by the two MCHC-Chlorin isomers, which are directly obtained from the synthetic route. The PS formulation was infused in the rabbit’s ear vein and eyes were immediately irradiated at 650 nm. Indirect ophthalmoscopy, fundus photography, fluorescein angiography and histopathological evaluations were used to evaluate levels of photo-thrombosis and collateral damage. Choriocapillary occlusion was achieved in all treated rabbits’ eyes, while retina and sclera were completely preserved. There was no photochemical reaction in none of the eyes that received LASER without PS. Both MCHC-Chlorin isomers were separately tested and exhibited similar positive results with no systemic toxicity. Therefore, PDT occurred equally well in all treated eyes and none of the controls showed any effect in the ophthalmological exams. MCHC-Chlorin offers great potential and should be further studied as an alternative drug for choroidal diseases.

Short-Term Choriocapillaris Changes in Patients with Central Serous Chorioretinopathy after Half-Dose Photodynamic Therapy.

Background: Although photodynamic therapy (PDT) has become the standard treatment for central serous chorioretinopathy (CSC), its mechanism of action remains unclear. It is assumed that PDT induces short-term choriocapillaris (CC) occlusion and long-term choroidal vascular remodeling. In this paper, we describe the short-term CC changes induced by Half-Dose PDT (HD-PDT) in chronic CSC using optical coherence tomography-angiography (OCTA). Methods: This is a prospective interventional case series. Chronic CSC eyes underwent Spectral-Domain OCT, Fundus Autofluorescence, FA, ICGA (Heidelberg Spectralis, Heidelberg, Germany) and OCTA (RTVue XR Avanti with AngioVue; Optovue Inc., Fremont, CA, USA) before HD-PDT, with follow-up after one hour, one week, and one month. Vascular changes after PDT were analyzed within the CC layer. The CC vessel density was defined as the percentage of an area occupied by flow pixels, using Image J software to obtain measurements by applying a grey level threshold. All pixels with a grey level above the threshold were considered as indicators of blood flow. Results: 20 eyes of 19 patients were included. At baseline the mean CC vessel density was 94.87 ± 2.32%. It significantly differed from the density at 1 week and 1 month (92.79 ± 3.16% and 95.55 ± 2.05%, p < 0.001, respectively), but not with values at 1 h (94.8 ± 2.28%, p = 0.516). Conclusions: CC vessel density was significantly reduced at 1 week as compared with baseline, suggesting a possible short-term effect of PDT on CC perfusion. After 1 month however, the CC vessel density was even higher than the baseline, probably due to a CC recovery. OCTA seems to be useful in the visualization of CC vessels and in confirming the mechanism of action of PDT treatment in eyes with chronic CSC.

Morphologic Choroidal and Scleral Changes at the Macula in Tilted Disc Syndrome with Staphyloma Using Optical Coherence Tomography

To evaluate the macular choroidal and scleral changes in tilted disc syndrome (TDS) with staphyloma using optical coherence tomography (OCT) to determine the mechanism of serous retinal detachment (SRD) formation. All eyes underwent fluorescein (FA) and indocyanine green angiography (ICGA) in this retrospective, observational study. Enhanced-depth imaging (EDI) OCT and prototype high-penetration (HP) OCT were used to examine the choroid and sclera, respectively, at the upper and lower optical areas and the subfovea on vertical OCT sections. Twenty-four eyes with TDS with inferior staphyloma were included. FA showed the macular area with the superior edge of staphyloma had a granular hyperfluorescent pattern and ICGA showed belt-like hypofluorescence. OCT showed SRDs in seven eyes. The mean EDI-OCT choroidal thicknesses in 19 eyes were: upper area, 211 ± 79 μm; subfovea, 153 ± 70 μm; and lower area, 158 ± 42 μm. The mean subfoveal and lower choroid were significantly (P < 0.01 for both) thinner than the upper area. The mean HP-OCT scleral thicknesses in 14 eyes were: upper area, 414 ± 36 μm; subfovea, 493 ± 40 μm; and lower area, 398 ± 83 μm. The subfoveal sclera was significantly (P < 0.01) thicker than the others. The subfoveal choroid was relatively thin and the subfoveal sclera thickened in TDS with a staphyloma edge at the macula. The area with retinal pigment epithelial (RPE) atrophy was hyperfluorescent on FA; choriocapillaris occlusion was hypofluorescent on ICGA. Characteristic anatomic subfoveal scleral alterations might lead to a thinner choroid and inhibit chorioscleral outflow; a secondary RPE disorder subsequently could cause SRDs.

Reply

Munier, Francis L MD*; Beck-Popovic, Maja MD†; Balmer, Aubin MD*; Gaillard, Marie-Claire MD*; Bovey, Etienne MD*; Binaghi, Stefano MD‡ Author Information

Indocyanine green infrared fluorescence angiography and histopathological correlation in experimental choroidal circulatory disturbance: Report 2

We performed an experimental study on choroidal circulatory disturbance to clarify basic problems about interpretation of retino-choroidal lesions in indocyanine green fluorescence angiography (ICG angiography). We severed the posterior ciliary arteries to produce choroidal circulatory disturbance. Fluorescein angiography and ICG angiography were performed at one week, and one month after occlusion. These findings were compared with histopathological findings. One week after occlusion, the area of choroidal infarct showed occlusion of choriocapillaris and proliferation of the retinal pigment epithelial (RPE) cells, this area showed hypofluorescence in the early phase ICG angiography. The hypofluorescence area increased in the late phase. One month after occlusion, the lesion showed loss of choriocapillaris at the center and proliferation of fibroblast-like cells at the edge of the lesion. The subretinal strand showed hyperfluorescence in late phase ICG angiography. Proliferated RPE cells masked ICG fluorescence in the late phase. Fibroblast-like cells showed tissue staining. When reading ICG angiography, we have to take into account that the ICG angiogram is greatly modified by condition of the RPE.

Protective Effect of Intravitreal Bevacizumab and Sub-Tenon Triamcinolone Acetonide against Occlusion of Choriocapillaris Induced by Photodynamic Therapy

Purpose: To evaluate the protective effect of intravitreal bevacizumab (IVB) and sub-Tenon triamcinolone acetonide (TA) against choriocapillaris occlusion induced by photodynamic therapy (PDT). Methods: This prospective, nonrandomized, consecutive study included 80 eyes of 80 patients with polypoidal choroidal vasculopathy who underwent an initial PDT. The posttherapeutic follow-up periods were more than 3 months (mean, 9.3 months). Patients were divided into three groups consecutively: the PDT group included 21 eyes of 21 patients treated with only PDT, the TA group included 32 eyes of 32 patients treated with PDT and a sub-Tenon injection of 20 mg TA, and the IVB group included 27 eyes of 27 patients treated with PDT and an intravitreal injection of 1.25 mg bevacizumab. Indocyanine green angiography (ICGA) was performed before and 3 months after PDT. The degree of choriocapillaris occlusion was assessed in the marginal zone of the PDT area based on the background hypofluorescence seen on ICGA quantified by densitometry (Imagenet). Results: ICGA at 1 and 5 min showed hypofluorescence in the marginal zone in all eyes 3 months after PDT. The hypofluorescence became indistinguishable from the background fluorescence 15 min after treatment in some eyes; however, the relative hypofluorescence persisted in some cases. The rates of fluorescence intensity in the marginal zone compared to those in the untreated area, i.e. the percentage of baseline fluorescence, were 0.60, 0.65 and 0.73 at 1, 5 and 15 min after dye injection in the PDT group, respectively, 0.64, 0.68 and 0.82 in the TA group, and 0.64, 0.73 and 0.90 in the IVB group. The intensity of the fluorescence was significantly (p < 0.05) higher in the TA group at 15 min and in the IVB group at 1, 5 and 15 min compared with the PDT group. Conclusions: IVB and TA reduced choriocapillaris occlusion after PDT. IVB appeared to have a stronger protective effect than TA in this therapeutic regimen.

Long-term Choroidal Vascular Changes after Iodine Brachytherapy versus Transpupillary Thermotherapy for Choroidal Melanoma

To compare long-term choroidal vascular changes after iodine-125 brachytherapy (IBT) versus transpupillary thermotherapy (TTT) used as primary treatment of small choroidal melanoma. Ninety-five small choroidal melanomas were randomized: 49 eyes with TTT and 46 eyes with IBT alone. Fluorescein and indocyanine green angiography (ICGA) were performed at 3-month intervals during the first year, and every 6 months thereafter. Mean follow-up was 56.2 months (range, 24-118 months; SD, 22.6). Tumor regressed in 45 (92%) TTT-treated vs 45 (98%) IBT-treated eyes (p=0.397). Four TTT-treated and one IBT-treated tumor recurred. Occlusion of choriocapillaris was present in all TTT and IBT cases. Closure of medium and large choroidal vessels was observed in 17 (35%) TTT-treated vs 44 (96%) IBT-treated eyes (p<0.001). Choroidal vascular remodeling was detected in 20 (41%) TTT-treated and 16 (35%) IBT-treated eyes (p=0.693). Retinochoroidal anastomosis was present in 4 of the 37 (11%) TTT-treated eyes with patency of medium and large choroidal vessels, but never observed in the IBT-treated eyes, and was associated with tumor recurrence. Among IBT-treated eyes, segments of choroidal vascular wall ICG staining and choroidal aneurysmal changes were detected in 30 (65%) and 7 (15%), respectively. These changes were never detected in TTT-treated cases (p<0.0001 and p=0.015, respectively). The pattern of tumor choroidal vascular changes following IBT and TTT differs. TTT is less effective in closing all tumor vasculature. The role of long-term choroidal vascular remodeling observed after these two treatments needs longer follow-up.

Effects of photodynamic therapy on the choriocapillaris and retinal pigment epithelium in the irradiated area

To evaluate the effect of photodynamic therapy (PDT) on the choriocapillaris and retinal pigment epithelium (RPE) in the irradiated area surrounding choroidal neovascularization (CNV) during 12 months of follow-up. We reviewed the medical records, and indocyanine green angiography (IA), fluorescein angiography (FA), and fundus photographic findings of 72 eyes (72 patients) with CNV associated with age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). Patients were divided into three groups based on the number of PDT sessions. Twelve months after PDT, we evaluated the relationship between the number of sessions and both the presence of hypofluorescence in the late phase of IA and window defects observed on FA in the irradiated areas. Twenty-three patients had one PDT session (group I), 25 had two (group II), and 24 had three or four (group III). IA revealed hypofluorescence indicating a choriocapillaris filling defect within the irradiated area in 11 eyes (48%) in group I, 18 (72%) in group II, and 22 (91%) in group III. The correlation between the number of PDT sessions and hypofluorescence in the irradiated areas was significant. FA showed window defects surrounding CNV in 26%, 52%, and 71% of eyes from groups I, II, and III, respectively. Subretinal hemorrhages had been present in 23 eyes (32%) and exudation in 13 (18%) prior to PDT. Areas without hemorrhages or exudation prior to PDT had a normal appearance within the irradiated area in all 72 eyes. Although the RPE in the irradiated area was preserved, 12 months after PDT, mild choriocapillaris occlusion was detected in the irradiated area in eyes that had undergone multiple PDT sessions.

Evaluation of the New Photosensitizer Stakel (WST-11) for Photodynamic Choroidal Vessel Occlusion in Rabbit and Rat Eyes

To evaluate the photodynamic potential of a new hydrosoluble photosensitizer (WST-11, Stakel; Steba Biotech, Toussus-Le-Noble, France), for use in occlusion of normal choroidal vessels in the rabbit eye and CNV (choroidal neovascularization) in the rat eye. Occlusive and nonocclusive parameters of Stakel and verteporfin photodynamic therapy (PDT) were investigated in pigmented rabbits. Eyes were followed by fluorescein angiography (FA) and histology at various intervals after PDT. When occlusive parameters (fluence of 50 J/cm(2), 5 mg/kg drug dose and DLI [distance to light illumination] of 1 minute) were used, Stakel PDT was efficient immediately after treatment without associated structural damage of the RPE and retina overlying the treated choroid in the rabbit eye. Two days later, total occlusion of the choriocapillaries was seen in 100% of the treated eyes, along with accompanying histologic structural changes in the overlying retina. When the occlusive parameters (fluence, 100 J/cm2; drug dose, 12 mg/m2; and DLI, 5 minutes) of verteporfin PDT were used, occlusion of the choriocapillaries was observed in 89% of the treated eyes. Histology performed immediately after treatment demonstrated structural damage of the overlying retina and RPE layer. Weaker, nonocclusive Stakel PDT parameters (25 J/cm2, 5 mg/kg, and DLI of 10 minutes) did not induce choriocapillary occlusion or retinal lesions on FA or histology. Weaker, nonocclusive verteporfin PDT parameters (10 J/cm2, 0.2 mg/kg, and DLI of 5 minutes) did not induce choriocapillary occlusion. However, histology of these eyes showed the presence of damage in the retinal and choroidal tissues. Moreover, preliminary results indicate that selective CNV occlusion can be achieved with Stakel PDT in the rat eye. Unlike verteporfin PDT, Stakel PDT does not cause direct damage to the RPE cell layer or retina. These observations indicate that Stakel PDT may have a high potential for beneficial therapeutic outcomes in treatment of AMD.

Experimental selective choriocapillaris photothrombosis using a modified indocyanine green formulation

Background:This in vivo study assessed and compared the effectiveness of an aqueous indocyanine green (ICG) formulation (R-ICG) and a lipid ICG formulation (L-ICG) in occluding the rabbit choriocapillaris, and determined...

Indocyanine green angiographic findings of hypertensive choroidopathy.

To evaluate fundus lesions in patients with malignant hypertension with indocyanine green angiography (ICGA). Cases of hypertensive choroidopathy were followed prospectively with ICGA, fluorescein angiography (FA), and optical coherence tomography (OCT). In Case 1, a 34-year-old man had a 10-day history of blurred vision in both eyes. Visual acuity was 0.2 in the right eye and 0.01 in the left eye. Blood pressure (BP) was 270/178 mmHg, and laboratory tests disclosed severe renal dysfunction. In Case 2, a 31-year-old man had noticed blurred vision in both eyes. Visual acuity was 1.2 in the right eye and 1.0 in the left eye. BP was 272/180 mmHg. Marked optic edema, retinal hemorrhage, cotton-wool patches, and Elschnig spots were seen in both cases. FA showed poorly perfused choroid in the early phase and fluorescein dye leakage from the optic disk. OCT demonstrated serous retinal detachment in both cases. ICGA revealed Elschnig spots corresponding to the patchy choroidal filling defect. ICGA demonstrated a larger area of choroidal filling defect than FA. In Case 1, ICGA revealed dye leakage from large choroidal vessels. These OCT and ICGA findings reduced after early systemic treatment for malignant hypertension. Hypofluorescent spots in the choroid thought to be choriocapillaris occlusion and choroidal vessel damage recover as result of early treatment for malignant hypertension. ICGA is useful to reveal the disturbance of choroidal circulation in hypertensive choroidopathy.

Effect of posterior juxtascleral triamcinolone acetonide on the efficacy and choriocapillaris hypoperfusion of photodynamic therapy

To evaluate the effect of posterior juxtascleral triamcinolone acetonide (TA) injection combined with photodynamic therapy with verteporfin (PDT) for treating exudative age-related macular degeneration (AMD), the best-corrected visual acuity (BCVA), the retreatment rates and the rate of choroidal hypoperfusion were investigated. A total of 67 eyes with subfoveal choroidal neovascularization (CNV) due to AMD were included. Forty-four eyes underwent PDT alone (PDT-alone group), and 23 eyes underwent PDT with the posterior juxtascleral injection of TA (PDT+TA group). Every 3 months after the PDT, the eyes were evaluated with regard to BCVA and requirement for retreatment by fluorescein angiography (FA) with the aid of optical coherence tomography (OCT). Choroiocapillaris hypoperfusion was assessed by indocyanine green angiography (ICGA) at 3 and 12 months. All patients completed a 1-year follow-up. At the baseline, there was no difference in lesion type, size or visual acuity between the two groups. At 1 year, the change in BCVA was -0.0811 logarithm of the minimum angle of resolution (LogMAR) in the PDT-alone group, compared with -0.0432 logMAR in the PDT+TA group. There was no significant difference in the change in BCVA between the two groups (P = 0.6910). The PDT+TA group required a lower mean number of treatments (1.64 compared with 2.34 [P = 0.0223]) and showed a higher rate of choriocapillaris occlusion at 3 months, but no significant difference at 1 year (P = 0.9243) Fewer retreatments were required in the TA+PDT group. There was no significant difference in the change in BCVA between the two groups. Adjacent TA may promote short-term choriocapillaris hypoperfusion.

Autofluorescence imaging of acute syphilitic posterior placoid chorioretinitis.

To evaluate the autofluorescence findings of acute syphilitic posterior placoid chorioretinitis (ASPPC). Patients with ASPPC underwent complete ophthalmologic examinations, including biomicroscopy, fundus color photography, autofluorescence photography, and fluorescein angiography. As expected, the patients had a yellowish lesion in the posterior pole. However, the lesion appeared to have two components, a diffuse placoid yellow discoloration at the level of the retinal pigment epithelium (RPE) and focal yellow spots that appeared to lie on the RPE. The diffuse placoid yellow color change at the RPE level showed a slight generalized increase in autofluorescence admixed with tiny spots of decreased autofluorescence. The yellow collections in front of the RPE were intensely hyperautofluorescent. The placoid area showed fluorescein staining, while the yellow deposits blocked the background fluorescence. Treatment of syphilis caused resolution of the placoid changes with associated improvement in the autofluorescence and fluorescein abnormalities. Patients with ASPPC have autofluorescence abnormalities during the acute manifestations of the disorder that help in interpretation of the fluorescein angiographic findings. We found evidence that the RPE is primarily involved and there does not appear to be choriocapillaris occlusion in early lesions.

Choroidal vascular changes after transpupillary thermotherapy for choroidal melanoma

Objective To evaluate choroidal vascular alterations after transpupillary thermotherapy used as the sole treatment for choroidal melanoma. Design Prospective noncomparative interventional case series. Participants Forty-five eyes of 45 patients affected by malignant choroidal melanoma treated with transpupillary thermotherapy alone with more than 1 year of follow-up. Intervention Transpupillary thermotherapy was performed through a panfunduscopic contact lens using an 810-nm diode laser. Main outcome measures Dynamic/static fluorescein and indocyanine green angiography were performed at scheduled intervals (24 hours, at 3-month intervals during the first year, and every 6 months thereafter) after transpupillary thermotherapy. Visual acuity, clinical evaluation, fundus photographs, and ultrasonographic examination were also performed. Results The mean follow-up was 30.5 months (range, 12–54 months). Changes in the choroidal circulation were always confined within the treatment margins (except in one case) and characterized by occlusion of choriocapillaris (100%), patent medium and/or large choroidal vessels (76%), retinochoroidal anastomosis (11%), and progressive choroidal vascular remodeling (42%). Forty-one cases (91%) showed persistent clinical regression, and four cases (9%) recurred; recurrent cases showed retinochoroidal anastomosis. Conclusions Transpupillary thermotherapy is suggested as a new single therapeutic modality in the treatment of selected choroidal melanomas, but more precise eligibility criteria and longer follow-up are mandatory. Patent choroidal circulation, choroidal vascular remodeling, and anastomosis after transpupillary thermotherapy might be helpful to detect recurrent tumors.

Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes.

To determine the effects of photodynamic therapy (PDT) on choroidal and retinal structures of human eyes. One eye from each of three patients with large malignant melanomas of the uvea destined for enucleation received PDT using verteporfin according to the approved treatment recommendations for patients with age-related macular degeneration. Two laser spots and two light doses (50 J/cm(2) and 100 J/cm(2)) were applied in unaffected chorioretinal areas. The effects of PDT were assessed by fluorescein and indocyanine-green angiography. The eyes were enucleated 1 week later, fixed in buffered paraformaldehyde/glutaraldehyde solution, bisected along the laser spots, and processed for light and electron microscopy. In agreement with the clinical angiographic findings of hypofluorescence, a rather selective occlusion of the choriocapillary layer was observed in the 50-J/cm(2) PDT areas, whereas the 100-J/cm(2) PDT areas additionally revealed closure of deeper choroidal vessels and focal alterations of the retinal pigment epithelium. The overlying neurosensory retina, including photoreceptors and retinal capillaries, was well preserved in all PDT areas. Electron microscopy showed that alterations of the choriocapillary endothelium comprised swelling, shrinkage and fragmentation of endothelial cells, detachment from their basement membrane up to complete degeneration of the endothelial lining, leading to platelet aggregation, degranulation, and thrombus formation. Complete occlusion of capillary lumina by fibrin, thrombocytes, and cellular debris was observed. Remaining intact endothelial cells appeared to be reorganized into novel smaller vascular channels within occluded lumina. PDT with verteporfin at a dosage used clinically induces selective occlusion of the physiological choriocapillaris without affecting deeper choroidal, retinal, and optic nerve vessels or the overlying retinal pigment epithelium and neurosensory retina. The main mechanism of action appears to be vascular thrombosis induced by cytotoxic damage of endothelial cells and platelet activation. An increase in light dose enhances the occlusive effect with thrombosis within deeper choroidal layers and damage to the retinal pigment epithelium. However, photoreceptors remained intact at all light doses used.

Choriocapillaris photodynamic therapy using indocyanine green

PURPOSE: To evaluate the potential of photodynamic therapy using indocyanine green for occlusion of choroidal neovascularization, the authors studied efficiency and collateral damage of photodynamic therapy–induced photothrombosis in the rabbit choriocapillary layer. METHODS: Fundus photography, fluorescein angiography, and light and transmission electron microscopy were used to study the efficiency of photodynamic therapy–induced photothrombosis using indocyanine green as the photosensitizer, and to assess the resultant collateral damage. The delivery system consisted of a modified infrared diode laser tuned to 810 nm, near the maximum absorption peak of indocyanine green. RESULTS: Choriocapillary occlusion was achieved at indocyanine green doses of 10 and 20 mg/kg and a radiant as low as 6.3 J/cm 2. When photodynamic therapy was performed with indocyanine green doses of 10 mg/kg, damage to the neural retina was minimal. Only inner photoreceptor segments showed degeneration, probably secondary to choroidal ischemia. Bruch membrane remained intact. Retinal pigment epithelium was invariably damaged, as seen with other photosensitizers. Temporary occlusion of large choroidal vessels occurred at both dye doses. CONCLUSIONS: In this experimental study, photodynamic therapy using indocyanine green and 810-nm light irradiation produced endothelium-bound intraluminal photothrombosis, with preservation of the retinal architecture and minimal loss of visual cells. Membrane targetability, hydrophilic and fluorescent properties, and activation at 805 nm suggest indocyanine green as a potential photosensitizer for choroidal neovascularization. These combined considerations point toward further study of photodynamic therapy using indocyanine green for the treatment of choroidal vascular disease.

Choroidal hypoperfusion after surgical excision of subfoveal neovascular membranes in age-related macular degeneration.

To study the choroidal circulation after surgical excision of subfoveal choroidal neovascular membranes (SFCNVM) in age-related macular degeneration (ARMD). Twelve eyes of eleven patients with ARMD that underwent surgical excision of SFCNVMs were evaluated with stereoscopic color fundus photography, stereoscopic fluorescein angiography (FA) and scanning laser ophthalmoscope-indocyanine green videoangiography (SLO-ICGv). The patients were followed for a mean of 7.9 months (range 2 to 14 months). Preoperatively, all eyes had angiographic evidence of a SFCNVM, with SLO-ICGv showing the presence of a choriocapillary blush. Postoperatively, stereoscopic color fundus photographs documented that the bed of the surgical excision was characterized by an absence of visible retinal pigment epithelial (RPE) pigmentation in all eyes. Stereoscopic FA of the excision bed revealed choriocapillary hypofluorescence with visible dye perfusion in the underlying medium and large choroidal vessels in all eyes. SLO-ICGv of the excision bed disclosed the presence of perfused medium and large choroidal vessels, but a marked choroidal hypofluorescence with loss of the choriocapillary and small choroidal vascular filling within the excision bed in eleven of the twelve eyes. Our results indicate that both choriocapillary and small choroidal vascular filling is frequently abnormal or absent in the bed of surgically excised subfoveal neovascular membranes in ARMD. This finding, which may represent either pathologic or iatrogenic choriocapillary and small choroidal vascular atrophy or occlusion with preservation of perfusion in the underlying medium and large choroidal vessels, may influence structural and visual recovery after submacular surgery for ARMD, despite RPE transplantation or regeneration.

Vascular Targeting in Photodynamic Occlusion of Subretinal Vessels

To evaluate the potential of photodynamic therapy (PDT) using benzoporphyrin derivative (BPD) for occlusion of subretinal neovascular membranes, the authors studied efficiency and collateral damage of PDT-induced photothrombosis in the rabbit choriocapillary layer. Benzoporphyrin derivative, a new photosensitizer, currently in clinical trials for tumor therapy, was used. Low-density lipoprotein served as a carrier to enhance selective targeting of vascular endothelial cells. Complete choriocapillary occlusion was achieved at a BPD dose of 2 mg/kg and a radiant exposure as low as 10 J/cm2. When PDT was performed 3 hours after BPD application, damage to the neural retina was minimal. Only inner photoreceptor segments showed mitochondrial swelling probably secondary to choroidal ischemia. Bruch's membrane remained intact. Retinal pigment epithelium was invariably damaged as seen with other photosensitizers. Compared with photocoagulation BPD-PDT allows endothelial-bound intraluminal photothrombosis, sparing important structures such as neural retina and Bruch's membrane. It may thus provide a more selective treatment of juxtafoveal and subfoveal neovascular membranes.

Pathophysiology of Hypertensive Retinopathy

The effects of systemic hypertension on the posterior segment of the eye are discussed under the headings of hypertensive choroidopathy, hypertensive retinopathy, and hypertensive optic disc edema. The sympathetic nervous control and autoregulatory mechanisms of the retinal and chorodial vasculatures are briefly reviewed. In hypertensive choroidopathy focal occlusion of choriocapillaris leads to necrosis of retinal pigment epithelium (Elschnig spots). Hypertensive retinopathy is described in vasoconstrictive, exudative, and sclerotic phases, followed by complications of the sclerotic phase. Hypertensive optic disc edema is influenced by the blood supply and extracellular tissue fluid pressure of the optic nervehead. In baboons with hypertensive disc edema, accumulation of axoplasmic components is observed in the optic nervehead.