Changes in choriocapillaris and retinal morphology after laser photocoagulation by OCT angiography: A case report.

RATIONALE: Earlier studies have shown that laser photocoagulation treatments are associated with good long-term visual acuity in most patients with severe nonproliferative diabetic retinopathy (S-NPDR). Histopathologic studies of autopsied eyes have demonstrated defects in the choriocapillaris beneath the retinal laser lesions secondary to photocoagulation for S-NPDR. These lesions have been observed to expand centrifugally over time especially in the posterior pole, and the atrophy of the retinal pigment epithelium (RPE) can be significantly enlarged. There are, however, limited studies detailing the in vivo changes that occur in the RPE and choriocapillaris following laser photocoagulation. PATIENT CONCERNS: A 46-year-old woman presented with visual disturbances in both eyes. DIAGNOSES: Fundus examinations showed many retinal hemorrhages and soft exudates in the four quadrants due to S-NPDR. INTERVENTIONS: Laser photocoagulations with a 532-nm wavelength argon laser with power of 170 to 230 mW and spot size of 200 µm were performed to treat the S-NPDR. The changes in the choriocapillaris and retinal vasculature were followed by optical coherence tomography (OCT) angiography. OUTCOMES: The choriocapillaris beneath the laser spots was disrupted from 1 hour following the photocoagulation but it was restored at week 2. The choriocapillaris appeared almost normal at some laser spots, but they were still some spots that were altered at 1 year. The outer retina and RPE were disrupted beneath the laser spots at 1 year. On the contrary, there were no visible retinal vascular changes in the superficial and deep plexuses of retinal vasculature determined by OCT angiography with manual and automated segmentation. LESSONS: The choriocapillaris in human eyes can recover after laser photocoagulation although the outer retina and RPE remain disrupted and do not recover.

Development of a surgical approach for a wide-view suprachoroidal retinal prosthesis: evaluation of implantation trauma.

BACKGROUND: Our research goal is to develop a safe, reproducible surgical approach for implantation of a wide-field retinal stimulating array. The aim of this study was to evaluate the pathological response to acute implantation of a functional prototype electrode array in the suprachoroidal space. METHODS: The surgical techniques to implant a 72 platinum electrode array fabricated on 8 × 13 × 0.4 mm polyimide and silicone substrate were developed in a pilot study in anesthetized cats. For the main study, nine eyes were implanted in vivo and unoperated eyes were used as controls. Surgery consisted of a temporal approach with a full-thickness scleral incision 5 mm posterior to the limbus. A suprachoroidal "pocket" was created, the electrode array inserted to sit beneath the area centralis, and placement was confirmed visually. The eyes were collected subsequently for histopathology. RESULTS: The array was consistently inserted into the suprachoroidal space beneath the area centralis in nine eyes. There was a significant hemorrhage in two cases where implantation was complicated by choroidal congestion. Retinal folding occurred only when the array tip was within 2.6 mm of the optic disc (p < 0.01). There was choroidal incarceration at the incision in six eyes and scleral distortion at the array edges in five. No cases were found where the implant breached the retina, choroid, or sclera. CONCLUSIONS: A large stimulation array can be reliably inserted into the suprachoroidal space without trauma to the neuroretina. These findings suggest that this is an appropriate surgical approach for the placement of an electrode array for use in retinal stimulation.

Early results of suprachoroidal drainage tube implantation for the surgical treatment of glaucoma.

PURPOSE: To evaluate the efficacy and safety of suprachoroidal silicone tube shunt implantation in glaucoma. PATIENTS AND METHODS: Twenty-four glaucomatous eyes unresponsive to medical treatment were included, 7 of them had earlier trabeculectomy. After preparation of a limbus-based scleral flap, 1.5 mm deep sclerotomy was made adjacent to scleral flap opening. Posterior end of the silicone tube was placed posteriorly in suprachoroidal space, anterior end was placed into anterior chamber. Intraocular pressure (IOP) and best corrected visual acuities (BCVA) were measured preoperatively and postoperatively on the first day, at the first week, in the first, third, sixth, twelfth, and eighteenth months. Postoperative IOP >21 mm Hg, <5 mm Hg (after 3 months), or additional glaucoma surgery were accepted as failure. Eyes not failed and not on supplemental medical therapy are considered as complete success. Eyes that have not failed, with or without supplemental medical therapy, are considered as qualified success. Hypotony was defined as early, when IOP below 5 mm Hg was observed within 4 weeks. RESULTS: Mean postoperative follow-up period was 34.4±23.7 weeks (range 4 to 78 wk). Complete success rates were 95.8%±4.1 at the first week, 79.2%±8.3 in the first and the third month, 63.3%±12.0 for the sixth and twelfth month. Qualified success rates were 95.8%±4.1 in the first week, 87.5%±6.8 in the first, third, sixth, twelfth months. Mean postoperative IOP's (8.5±4.9mm Hg, 12.9±5.6 mm Hg, 17.0±7.9 mm Hg, 15.3±3.6 mm Hg, 18.3±6.0, 15.1±6.0 mm Hg, respectively for the first week, first, third, sixth and twelfth mo) were significantly lower than preoperative mean IOP's. The success rates in cases without earlier trabeculectomy were significantly higher than in cases with earlier trabeculectomy (P=0.035). Postoperative first day mean±SD BCVA value was significantly lower than preoperative value (P=0.004). Failure was seen in 7 eyes of which 3 of them underwent reoperation for glaucoma. Early hypotony was seen in 6 eyes. No infection, choroidal, or retinal detachment was seen. There was a fibrin reaction in the anterior chamber in 3 patients. Two patients had intracameral bleeding, 1 of them underwent anterior chamber lavage. CONCLUSIONS: Suprachoroidal tube drainage of aqueous humor from the anterior chamber to the suprachoroidal space is effective in reducing IOP in glaucoma patients, with lower serious complication rates, and may be preferred as initial surgery in cases without earlier trabeculectomy.

[Basic principles and clinical application of retinal laser therapy]. / Grundlagen und klinische Anwendung der Lasertherapie an der Netzhaut.

The scientific background of laser photocoagulation of the ocular fundus was studied extensively by several investigators in the 1970 s and 1980 s. The basic principles were successfully resolved during that time and clinical consequences for proper application of the laser photocoagulation for various diseases were deduced. The present paper gives an overview about the physical basics of laser-tissue interactions during and after retinal laser treatment and the particular laser strategies in the treatment of different retinal diseases. Thus, it addresses the issue of the impact on tissue of laser parameters as wavelength, spot size, pulse duration and laser power. Additionally, the different biological tissue reactions after laser treatment are presented, such as, e. g., for retinopexia or macular treatments as well as for diabetic retinopathies. Specific laser strategies such as the selective laser treatment of the RPE (SRT) or the transpupillary thermotherapy (TTT) are presented and discussed.

Efficacy of supra-choroidal, bipolar, electrical stimulation in a vision prosthesis.

The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 +/- 29.85 nC.

Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice.

PURPOSE: To investigate the role of eicosapentaenoic acid (EPA), the major omega-3 polyunsaturated fatty acid (PUFA), in the development of choroidal neovascularization (CNV), together with underlying molecular mechanisms. METHODS: Six-week-old C57BL/6 mice were fed with laboratory chow with 5% EPA or the omega-6 PUFA linoleic acid (LA) for 4 weeks. Laser photocoagulation was performed to induce CNV, and the volume of CNV tissue was evaluated by volumetric measurements. The expression and production of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, vascular endothelial growth factor (VEGF) and interleukin (IL)-6 in the retinal pigment epithelium (RPE)-choroid in vivo, and stimulated b-End3 endothelial cells and RAW264.7 macrophages in vitro were evaluated by RT-PCR and ELISA. Fatty acid composition in the serum and the RPE-choroid was analyzed by gas chromatography and high-performance liquid chromatography, respectively. Serum levels of C-reactive protein (CRP), IL-6, VEGF, MCP-1, and soluble ICAM-1 were examined by ELISA. RESULTS: The CNV volume in EPA-fed animals was significantly suppressed compared with that in control mice, whereas the LA-rich diet did not affect CNV. The mRNA expression and protein levels of ICAM-1, MCP-1, VEGF, and IL-6 after CNV induction were significantly reduced in EPA-supplemented mice. In vitro, EPA application led to significant inhibition of mRNA and protein levels of ICAM-1 and MCP-1 in endothelial cells and VEGF and IL-6 in macrophages. EPA-fed mice exhibited significantly higher levels of EPA and lower levels of the omega-6 PUFA arachidonic acid in the serum and the RPE-choroid than control animals. EPA supplementation also led to significant reduction of serum levels of IL-6 and CRP after CNV induction. CONCLUSIONS: The present study demonstrates for the first time that an EPA-rich diet results in significant suppression of CNV and CNV-related inflammatory molecules in vivo and in vitro. These results suggest that frequent consumption of omega-3 PUFAs may prevent CNV and lower the risk of blindness due to age-related macular degeneration.

Laboratory investigation of microelectronics-based stimulators for large-scale suprachoroidal transretinal stimulation (STS).

This paper describes the technological developments underlying the realization of a reliable and reproducible microchip-based stimulator with a large number of stimulus electrodes. A microchip-based stimulator with over 500 electrodes for suprachoroidal transretinal stimulation (STS) is proposed in this paper, and an example is presented. To enhance reliability and reproducibility for such a large array, we introduce a flip-chip bonding technique and place microchips on the reverse side of a substrate. A square microchip of size 600 microm was fabricated using 0.35 microm standard CMOS process technology. Twelve microchips were flip-chip bonded on a polyimide substrate through Au bumps. To evaluate the feasibility of the proposed device, we successfully fabricated a stimulator with 12 microchips and 118 electrodes made of Pt/Au bumps, and demonstrated their operation in a saline solution for 2 weeks. Also, to evaluate the device operation in vivo, a stimulator with one active IrO(x) electrode was implanted into the scleral pocket of a rabbit and electrical evoked potential (EEP) signals with a threshold of 100 microA were obtained. We also fabricated a simulator with 64 microchips that has 576 electrodes (9 electrodes in a microchip times 64 microchips).

Transpupillary thermotherapy (TTT) with short duration laser exposures induce heat shock protein (HSP) hyperexpression on choroidoretinal layers.

BACKGROUND AND OBJECTIVES: To assess a choroidal heat shock protein hyperexpression after transpupillary thermotherapy (TTT) performed with exposures shorter than 60 seconds. STUDY DESIGN/MATERIALS AND METHODS: Nine male pigmented rabbits were anesthetized and TTT was performed on their right eye with a 810 nm diode laser (Iridis, Quantel-Medical (France)) (spot size: 1.3 mm). Three exposure durations (60, 30, or 15 seconds) were used with three ranges of power for each duration ("high," "mild," or "low"). A series of laser impacts was delivered to the posterior pole of the retina. Left eyes were used as controls. Twenty-four hours after laser irradiation, the animals were killed and histological study was performed on chorioretinal layers. Tissue samples were fixed in formalin and embedded in paraffin. A monoclonal antibody was used to detect Hsp70 immunoreactivity (mouse IgGl, SPA-810, Stress Gen, Victoria, BC, Canada), followed by a biotinylated goat anti-mouse antibody (Dako, Glostrup, Denmark), revealed by the avidin-biotin complex (Vectastain kit, Vector Laboratries, Burlingame, CA, USA) and the AEC chromogen. Retinal structures were further identified by HES coloration. RESULTS: During the experiments, the laser spots were not visible except for the strongest "high" powers for each exposure duration, where a whitening was discernable at the end of the laser exposures. A strong HSP70 immunoreactivity was detected in choroidal, non-pigmented cells for laser exposures lasting 60, 30, or 15 seconds with "mild" laser powers. On the contrary, rare HSP hyperexpression was detected with "high" or "low" laser powers lasting 60, 30, or 15 seconds. No HSP-70 immunoreactivity was detected on control eyes nor outside of the irradiated zones of treated eyes. CONCLUSIONS: Transpupillary laser irradiation lasting 15, 30, or 60 seconds induces an hyperexpression of HSP on choroidal layers. This could be a basis for the use of TTT with "short" laser exposures.

Diode laser modifications for treatment of choroidal neovascularisation.

The aim of this paper is to describe various diode laser modifications and their use in treating choroidal neovascularisation in age-related macular degeneration. Diode lasers are used to treat selected choroidal neovascular membranes. Alterations in microprocessor connectivity, and parameters such as maximum spot size, light delivery time and coupled Joule meter, were made so that ophthalmic surgeons could specify treatment possibilities. A trimodal (photocoagulation, transpupillary thermotherapy and photodynamic therapy) application laser device coupled to a single light source has been developed. The new diode laser modifications were technically successful. Microprocessor connectivity was obtained, larger spot sizes were achieved, light delivery time could be extended and energy parameters were available at the display.

Inhibitory effect of TNP-470 on experimental choroidal neovascularization in a rat model.

PURPOSE: To determine whether an angiogenic inhibitor, TNP- 470 (TNP), an analogue of fumagillin, inhibits choroidal neovascularization (CNV) induced by diode laser photocoagulation in a rat experimental model. METHODS: Fundus laser photocoagulation was performed on Brown Norway rats to induce CNV. In the treatment group, TNP was administered intraperitoneally at the time of laser photocoagulation and on day 7 (50 mg/kg at each time). The incidence of CNV formation was evaluated by fluorescein angiography. The retina was collected from the rats on days 1, 3, 7, and 14 after laser photocoagulation, and semiquantitative polymerase chain reaction (PCR) analyses for the expression of mRNA of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were carried out. Localization of bFGF mRNA was studied by in situ reverse transcription-PCR (RT-PCR). The numbers of positively labeled cells for bFGF mRNA were compared between the TNP treatment and control groups. RESULTS: The incidence of CNV formation was 22.7% in the TNP-treated rats and that in the control rats was 61.4% (P < 0.001). The semiquantitative PCR analyses showed that bFGF mRNA was upregulated on days 3 and 7 in the control rats, but no significant changes were found in TNP-treated rats. There was no detectable difference in VEGF gene expression between the control and TNP-treated rats. bFGF mRNA was detected by in situ RT-PCR in the regenerated retinal pigment epithelial cells and cells of the outer and inner nuclear layers of the control rats. The number of positive cells for bFGF mRNA in the TNP treatment group was significantly smaller than that of the control group (P < 0.05) on days 3 and 14. CONCLUSIONS: TNP- 470 treatment reduced the incidence of laser-induced CNV formation in this experimental model. The expression of bFGF associated with CNV formation was also significantly reduced by the TNP treatment.