[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.

A prospective randomised study on low-dose transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration.

AIM: To compare the efficacy of low-dose transpupillary thermotherapy (TTT) and verteporfin photodynamic therapy (PDT) in patients with occult neovascular age-related macular degeneration (AMD). METHODS: Patients were randomised to receive either low-dose TTT (136 mW/mm) (and sham PDT) (n = 52) or PDT (and sham TTT) (n = 46) with retreatment if leakage was documented by fluorescein angiography. At baseline and at every follow-up, best corrected visual acuity (BCVA) was measured with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, lesion size on fluorescein angiography and foveal thickness with optical coherence tomography. The primary outcome measure was the proportion of patients who lost <15 letters at 12 months' follow-up. Secondary outcome measures included the proportion of patients who gained >/=0 letters, the change in mean lesion size and the change in foveal thickness at 12 months' follow-up. RESULTS: The percent of patients losing fewer than 15 letters at 12 months was 75.0% in the TTT group and 73.9% in the PDT group (p>0.05). The percent of patients with preserved or improved BCVA was 36.5% in the TTT group versus 23.9% in the PDT group (p>0.05). The mean decrease in foveal thickness was 15% for TTT and 24% (p>0.05) for PDT-treated patients, and the mean increase in total lesion area was -0.7% and -1.1% (p>0.05), respectively. CONCLUSION: In this prospective, randomised trial low-dose TTT and PDT appeared to be equally efficient at stabilising visual acuity in patients with occult neovascular AMD. Low-dose TTT may be considered as an alternative to PDT in this set of patients and also as an adjuvant to pharmacotherapy.

[Transpupillary thermotherapy for occult choroidal neovascularizations]. / Transpupillare Thermotherapie bei okkulten subretinalen Neovaskularisationen.

PURPOSE: This contribution describes the results of transpupillary thermotherapy (TTT) for age-related exudative macular degeneration (AMD) with regression. PATIENTS AND METHODS: In exudative AMD with occult choroidal neovascularization (CNV), transpupillary thermotherapy (TTT) was performed using a diode laser (Iridex) in unselected patients. Before therapy and 1, 3, and 6 months after the initial treatment the patients were examined clinically. Additionally threshold testing in the 10 degrees field (Humphrey) and fluorescein angiographies were documented at all check-ups. RESULTS: With respect to vision, differences in the slope of the regression lines between small, medium, and large CNV were significant (p<0.001). The slope of the regressions lines was significant except for small CNV. Regarding the 10 degrees field (Humphrey), there were no statistical differences in the slope of the regression lines (p=0.867). CONCLUSIONS: Transpupillary thermotherapy with small CNV did not show a statistically significant decrease of VA. Thus, in clinical terms early treatment of occult CNV with TTT seems to be able to prevent a further loss of visual acuity.

Chorioretinal temperature monitoring during transpupillary thermotherapy for choroidal neovascularisation.

AIMS: To investigate the difference in temperature rise between normal choroid and choroidal revascularisation (CNV) during transpupillary thermotherapy (TTT) and the relation between laser spot size and power in the rat fundus. METHODS: A modified slit lamp, which was installed with two laser wavelengths (490 nm for illumination and fluorescein excitation and 810 nm for hyperthermia), was developed for TTT and temperature monitoring. Temperature rise during TTT was monitored by observing fluorescence released from thermosensitive liposomes encapsulating carboxyfluorescein. Two types of liposomes were prepared; their phase transition temperatures were 40 degrees C and 46 degrees C, respectively. Laser power settings required to observe fluorescence released from 46 degrees C liposome in normal choroid or CNV were compared. Next, the power settings with 0.5 mm and 0.25 mm spot sizes were compared following administration of 40 degrees C liposome or 46 degrees C liposome. RESULTS: The minimum power values when release from 46 degrees C liposome was observed showed a significant difference in distribution of power values between normal choroid and CNV. CNV required significantly higher power than normal choroid. With 40 degrees C liposome, the power was 9.7 (1.9) mW (mean (SD)) at a spot size of 0.25 mm, and 12.1 (1.6) mW at 0.5 mm, respectively. When using 46 degrees C liposome, the power setting was 10.2 (1.2) mW at a spot size of 0.25 mm, and 14.6 (2.2) mW at 0.5 mm, respectively. CONCLUSIONS: CNV demonstrated varying heat conduction, compared with normal choroid. Laser power required to raise the temperature should not necessarily be doubled, even when the spot size is doubled. Close attention should be given to the selection of power settings when performing TTT for CNV.

Evaluation of trans-scleral diode laser using diopexy probe for subfoveal choroidal neovascular membrane in age-related macular degeneration.

OBJECTIVE: To evaluate safety and short-term visual and fluorescein angiographic effects of trans-scleral diode laser photocoagulation in patients with subfoveal choroidal neovascularization from age-related macular degeneration (ARMD). BACKGROUND DATA: The visual outcome following treatment of subfoveal choroidal neovascularization in ARMD is still unsatisfactory. Various forms of therapy such as laser treatment, photodynamic therapy, radiation therapy, transpupillary thermotherapy, and surgical excision have been tried with variable results. MATERIALS AND METHODS: Patients with subfoveal choroidal neo-vascularization were treated with trans-scleral diode laser using the diopexy probe under indirect ophthalmoscopic visualization and followed up at 2, 6, and 12 weeks. Standardized protocol refraction, visual acuity testing, reading speed, contrast requirement measurement, ophthalmic examinations, color fundus photographs, and fluorescein angiogram were used to evaluate the results of treatment. RESULTS: Eighteen eyes of 18 patients were included in the study between April 2000 and May 2002. At 12 weeks, 81.5% patients showed stabilization (+/-5 letters) in letter visual acuity score, and one patient showed improvement (gain of more than five letters) in letter visual acuity score. Reading speed levels and contrast requirement were found to be similar to pre-laser level at 3 months followup. At 12 weeks, moderate fluorescein leakage was seen in one eye, minimal leakage was seen in five eyes, absence of leakage was seen in 10 eyes, and progression was seen in two eyes. CONCLUSION: Transcleral diode laser treatment of subfoveal choroidal neovascular membranes in ARMD may be an effective as well as safe alternative in the management of these patients.

New treatments in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in individuals 50 years and older in the developed world. Choroidal neovascularization (CNV) in exudative AMD is responsible for the majority of severe vision loss. Until recently, laser photocoagulation was the only well-established and widely accepted treatment for CNV. However, it is beneficial only for a small subset of patients, has a high rate of CNV persistence and recurrence and results in iatrogenic, collateral damage to the overlying retina. These issues make it difficult to recommend in the case of subfoveal lesions. Consequently, numerous experimental therapeutic interventions are under investigation with the common objective of destroying the CNV but leaving the foveal neurosensory retina intact. Treatment modalities can be grouped into five major categories: photodynamic therapy; radiotherapy; transpupillary thermotherapy; anti-angiogenic and angiostatic agents; and surgical intervention. The present review aims to explain the rationale behind these new treatments, analyse the evidence for their safety and efficacy, determine their stage of development and indicate in which patients they are potentially useful.

[The role of surgery in the treatment of age-related macular degeneration]. / Place de la chirurgie dans le traitement de la DMLA.

The place of surgery in DMLA amounts to the surgical treatment of choroidal neovascular membranes and submacular hemorrhage. After a brief historical review, the different techniques currently used are described, but indications have become rarer since the development of dynamic phototherapy. However, despite a high complication rate, these surgical methods should not disappear from our therapeutic arsenal because they have proved their ability to restore good visual acuity.

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.

Subthreshold infrared footprinting with indocyanine green for localizing low-intensity infrared photocoagulation.

A novel technique for localizing subthreshold infrared (810 nm) laser treatment and its use in three patients is described. Two patients were treated for choroidal neovascularization with transpupillary thermotherapy or focal subthreshold photocoagulation, and the third patient was treated with grid laser photocoagulation for diabetic macular edema using the 810-nm laser after undergoing indocyanine green angiography for diagnostic purposes. Postoperative indocyanine green images, obtained without reinjection of indocyanine green, revealed areas of hypofluorescence that corresponded to the laser treatment spots. This technique, named subthreshold infrared footprinting, can precisely localize subthreshold infrared laser photocoagulation sites and is potentially useful for evaluating treatment postoperatively and planning additional therapy if necessary.

[Age related macular degeneration surgery]. / Chirurgia degenerescentei maculare senile.

Age related macular degeneration (ARMD) is a disease in which the retinal pigment epithelium (RPE) is damaged in the central retinal area. In the exudative form, the vision loss is due to choroidal neovascularization, while in the nonexudative or atrophic form, there is a vision loss because of the retinal pigment epithelium atrophy. Treatment which proved to be efficient in lowering the risk of severe vision loss in the exudative form includes laser photocoagulation, photodynamic therapy, transpupilary thermotherapy and as surgical treatment, the controversial subretinal membrane extraction. In all these situations the RPE is damaged by the disease itself and by the therapeutic procedure too. Retinal translocation is a surgical procedure that intends to remove the neurosensory retina from an area with damaged RPE to an healthy RPE area, through a 360 degrees retinotomy or through a limited one. This paper present some ARMD cases treated by subretinal membrane extraction and one by limited retinal translocation. The question which is still remaining is which are the risks and benefits for the following treatment procedures: laser photocoagulation, photodynamic therapy, transpupilary thermotherapy and surgical approach?

Theoretical investigation of the role of choriocapillaris blood flow in treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration.

PURPOSE: To investigate the relationship between choriocapillaris blood flow and blood flow through an overlying choroidal neovascularization, as it relates to photocoagulation-induced changes in the choriocapillaris circulation. METHODS: A theoretical model that simulates the blood flow in the choriocapillaris and choroidal neovascularization of the human eye was developed, based on histologically determined vascular geometry and experimentally measured blood pressure gradients. The choriocapillaris blood pressure and blood flow were examined before and after simulated photocoagulation of various Sattler layer vessels entering the choriocapillaris in the vicinity of the choroidal neovascularization. (The Sattler layer is the inner layer of medium-sized choroidal vessels that includes both arterioles and venules that supply the choriocapillaris.) RESULTS: The theoretical model showed that both partial and complete occlusion of either Sattler arteriole or venous vessels in the vicinity of the capillary-like vessels connecting a choroidal neovascularization to the underlying choriocapillaris results in significant choroidal neovascularization blood flow reduction. These theoretical results are similar to clinically observed changes induced by laser photocoagulation of feeder vessels. (In this discussion, the term "feeder vessels" refers to those vessels in an indocyanine green angiogram image that appear to supply blood to a choroidal neovascularization; these vessels appear to be Sattler layer vessels, rather than the histologically demonstrated short, capillary-like vessels that form choriocapillaris-choroidal neovascularization communications.) CONCLUSIONS: Reduction of choriocapillaris blood flow underlying a choroidal neovascularization may be sufficient to reduce the blood flow rate in the choroidal neovascularization and thereby reduce the associated retinal edema. The results also suggest that reduction of choriocapillaris blood flow may be the common hemodynamic event associated with the successful application of several currently practiced methods of choroidal neovascularization treatment, including feeder vessel photocoagulation, photodynamic therapy, transpupillary thermotherapy, and prophylactic drusen photocoagulation. Ultimately, this model may be useful in determining optimal placement of laser photocoagulation burns to achieve a desirable perturbation in choroidal blood flow distribution and thereby reduce choroidal neovascularization blood flow to the extent necessary to obliterate associated retinal edema.

Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10.

BACKGROUND AND OBJECTIVE: To determine the optimal treatment parameters for selective occlusion of choroidal neovascularization (CNV) by photodynamic therapy (PDT) by using the photosensitizer ATX-S10 and a diode laser (wavelength = 670 nm). MATERIALS AND METHODS: Experimental CNV was induced in rat fundi by argon laser photocoagulation. The distribution of ATX-S10 in the chorioretina was analyzed by fluorescence microscopy, and the optimal treatment parameters for selective occlusion of CNV were investigated by changing the dosage and timing of laser irradiation. CNV closure and resulting damage of the surrounding tissue were documented by fluorescein angiography and light and electron microscopies. RESULTS: Fluorescence of ATX-S10 was observed to be localized in the vascular lumen of the retina and choroid within 5 min after dye injection and increased in intensity in CNV up to 2-6 h and decreased rapidly in normal tissue. Laser irradiation with radiant exposures of 7.4 J/cm2 applied immediately after dye injection or with 22.0 J/cm2 at 2-4 h later effectively occluded the induced CNV without causing significant damage to normal retinal capillaries and large choroidal vessels. CONCLUSIONS: PDT using ATX-S10 can selectively occlude CNV. ATX-S10 is a potentially useful photosensitizer for the treatment of CNV.