Subthreshold micropulse laser photocoagulation therapy in a case of bilateral retinal astrocytic hamartomas with tuberous sclerosis complex: A case report.

RATIONALE: Report a case of bilateral multiple retinal hamartomas (RAHs) in a patient with tuberous sclerosis complex (TSC) and introduced a new method (subthreshold micropulse laser photocoagulation) for the treatment of RAHs. PATIENT CONCERNS: A 20-year-old man with TSC complained of decreased vision and metamorphosia in both eyes for 2 months. At presentation, visual acuity (VA) was 20/32 in the right eye and 20/40 in the left eye. Fundus photographs, optical coherence tomography, fundus fluorescein angiography (FFA), and indocyanine green angiography indicated multiple RAHs in both eyes. DIAGNOSES: Bilateral retinal astrocytic hamartomas. INTERVENTIONS: In the right eye, 577 nm photocoagulation was adopted to treat the RAHs with obvious fluorescein leakage in FFA. The paramacular RAHs were treated by subthreshold micropulse mode to minimize the damage to macula. Photocoagulation therapy was administrated in the left eye after 1 dose of intravitreal ranibizumab treatment. OUTCOMES: After photocoagulation therapy (including subthreshold micropulse laser photocoagulation for the paramacular RAHs in both eyes), the VA improved to 20/25 OD and 20/32 OS with no recurrence of exudation. LESSONS: About 577 nm photocoagulation for the peripheral RAHs in combination with subthreshold micropulse laser photocoagulation for RAHs in the macular zone is a good option for multiple RAHs in patients with TSC.

A two-stage estimation in the Clayton-Oakes model with marginal linear transformation models for multivariate failure time data.

This paper considers the analysis of multivariate survival data where the marginal distributions are specified by semiparametric transformation models, a general class including the Cox model and the proportional odds model as special cases. First, consideration is given to the situation where the joint distribution of all failure times within the same cluster is specified by the Clayton-Oakes model (Clayton, Biometrika 65:141-151, l978; Oakes, J R Stat Soc B 44:412-422, 1982). A two-stage estimation procedure is adopted by first estimating the marginal parameters under the independence working assumption, and then the association parameter is estimated from the maximization of the full likelihood function with the estimators of the marginal parameters plugged in. The asymptotic properties of all estimators in the semiparametric model are derived. For the second situation, the third and higher order dependency structures are left unspecified, and interest focuses on the pairwise correlation between any two failure times. Thus, the pairwise association estimate can be obtained in the second stage by maximizing the pairwise likelihood function. Large sample properties for the pairwise association are also derived. Simulation studies show that the proposed approach is appropriate for practical use. To illustrate, a subset of the data from the Diabetic Retinopathy Study is used.

Likelihood ratio procedures and tests of fit in parametric and semiparametric copula models with censored data.

Copula models for multivariate lifetimes have become widely used in areas such as biomedicine, finance and insurance. This paper fills some gaps in existing methodology for copula parameters and model assessment. We consider procedures based on likelihood and pseudolikelihood ratio statistics and introduce semiparametric maximum likelihood estimation leading to semiparametric versions. For cases where standard asymptotic approximations do not hold, we propose an efficient simulation technique for obtaining p-values. We apply these methods to tests for a copula model, based on embedding it in a larger copula family. It is shown that the likelihood and pseudolikelihood ratio tests are consistent even when the expanded copula model is misspecified. Power comparisons with two other tests of fit indicate that model expansion provides a convenient, powerful and robust approach. The methods are illustrated on an application concerning the time to loss of vision in the two eyes of an individual.

Additive transformation models for clustered failure time data.

We propose a class of additive transformation risk models for clustered failure time data. Our models are motivated by the usual additive risk model for independent failure times incorporating a frailty with mean one and constant variability which is a natural generalization of the additive risk model from univariate failure time to multivariate failure time. An estimating equation approach based on the marginal hazards function is proposed. Under the assumption that cluster sizes are completely random, we show the resulting estimators of the regression coefficients are consistent and asymptotically normal. We also provide goodness-of-fit test statistics for choosing the transformation. Simulation studies and real data analysis are conducted to examine the finite-sample performance of our estimators.

Fundamentos del láser y su aplicación en la urología / The basics of laser and its application in urology

El láser, dispositivo de amplificación de luz por emisión estimulada de radiación, se trata de un dispositivo capaz de transformar otras energías en radiación electromagnética emitiendo haces de luz de distintas longitudes de onda. Se trata de aparatos que amplifican la luz y producen haces de luz coherentes cuya frecuencia va desde el infrarrojo hasta los rayos X. La emisión estimulada, proceso en que se basa el Láser, fue descrita por A. Einstein en 1917, pero no es hasta la década de los 60, cuando se observó el primer proceso láser en un cristal de rubí. Según el medio que emplean, los láseres suelen denominarse de estado sólido, de gas, semiconductores o líquidos. Los posibles usos del láser son casi ilimitados, convirtiéndose en una herramienta muy valiosa dentro de las Ciencias biomedicas, gracias a los diversos efectos (fotovaporización, fotodisrupción, fotocoagulación o fotoestimulación) que provoca al interactuar con los tejidos. Por este motivo, hoy día, el uso de láseres en el campo de la Urología nos ofrece un amplio abanico de posibilidades, que van desde la cirugía desobstructiva como la fragmentación de un cálculo o la resección y ablación del tejido prostático hasta la cirugía reconstructiva como es la soldadura de tejidos en la vasovasostomía o la reparación de una estenosis uretral (AU)

A laser, light amplification by stimulated emission of radiation, is a device able to transform other energies into electromagnetic radiation with emission of light beams of different wavelengths. They amplify the light and produce coherent light beams, the frequency of which varies from infrared to X ray. Stimulated emission, the process laser is based on, was described by A. Einstein in 1917, but it was not until the decade of the '60s when the first laser process was observed in a ruby crystal. Depending on the environment they use, lasers may be named as solid-state, gas, semiconductors or liquid. The possibility of uses for laser is almost unlimited, becoming a very valuable tool in biomedical sciences thanks to the various effects they produce when interacting with tissues (photovaporization, photodisruption, photocoagulation or photostimulation). For this reason, today, the use of lasers in the field of urology offers a wide range of possibilities, going from surgery for the treatment of obstruction, such as the fragmentation of a urinary stone or resection/ablation of prostatic tissue, to reconstructive surgery, such as tissue welding in vasovasostomy or urethral stenosis repair (AU)

[Proliferative diabetic retinopathy: vitreo-retinal complications are often related to insufficient retinal photocoagulation]. / Rétinopathie diabétique vasoproliférante: complications vitréorétiniennes et photocoagulation rétinienne incomplète.

INTRODUCTION: Panretinal photocoagulation proved to be effective in preventing complications related to vasoproliferative diabetic retinopathy. Surgery is most often a last resort in cases of recurrent or persistent vitreous hemorrhage or retinal detachment. The aim of our study is to point out that eyes requiring surgery for complications related to vasoproliferative diabetic retinopathy are often insufficiently photocoagulated. PATIENTS AND METHODS: Retrospective analysis of operating protocols and surgical results for a series of 39 eyes of 36 patients with complications of vasoproliferative diabetic retinopathy. RESULTS: The mean age at the intervention was 57 years. Eighty-five percent of the eyes had a vitreous hemorrhage, 17% a retinal detachment. Eighty-five percent of the eyes had undergone a partial retinal photocoagulation before surgery. All eyes underwent a vitrectomy with segmentation of fibrovascular membranes. In 85% of the eyes studied, endolaser photocoagulation was necessary, sometimes even in the mid-periphery. After 39+/-26 months of postoperative follow-up, 97% of eyes showed improvement of the anatomical state of the retina and improvement or stabilization of visual acuity. CONCLUSION: Our results confirm the benefit of vitreoretinal surgery in complications related to vasoproliferative diabetic retinopathy. Moreover, it should be emphasized that complications requiring surgery often result from incomplete preoperative photocoagulation. To be effective, photocoagulation has to destroy more than 35% and up to 50% of photoreceptors. An intraoperative laser extension can reduce the risk of regrowth of fibrovascular membranes.

Analysis of ulcer data using hierarchical generalized linear models.

In multi-centre clinical trials, heterogeneities in individual hospital treatment effects can be modelled as random effects. Estimates of the individual hospital treatment effects and estimate of the mean treatment effect, allowing for the presence of overall hospital differences, are required, together with some measure of their uncertainty. Systematic inferences from the hierarchical-likelihood are now possible, using hierarchical generalized linear models. We show how to construct profile likelihoods for the treatment effects of individual hospitals.

[Retinal detachment due to macular hole: therapeutic problems]. / Décollement de rétine par trou maculaire: problèmes thérapeutiques.

UNLABELLED: To compare the success rate and the visual improvement of different surgical techniques for treating 21 retinal detachments due to macular hole in highly myopic eyes. METHODS: Twelve patients were treated by gas tamponade alone, 5 patients underwent vitrectomy with gas tamponade, 4 patients underwent vitrectomy with epiretinal membrane pealing and gas or oil silicone tamponade. RESULTS: Fifty eight % of patients were successfully treated after gas tamponade alone, and 75% after vitrectomy, epiretinal membrane pealing and gas or silicone oil tamponade. After retreatment in 7 patients, the final reattachment rate was 80%. Visual acuity was inchanged in 12 cases, improved to 1/20-1/10 in 8 case and reached 3/10 in 1 case. CONCLUSION: A therapeutic scheme is suggested according to the type of retinal detachment, macular vitreoretinal traction and pigment epithelium and chorioretinal degeneration condition.

Light panretinal photocoagulation (LPRP) versus classic panretinal photocoagulation (CPRP) in proliferative diabetic retinopathy.

PURPOSE: We misled to verify whether a panretinal photocoagulation (PRP) performed using low levels of ARGON laser energy (light PRP) has the same efficacy as a PRP performed in a conventional fashion using argon green wavelengths (classic PRP) in eyes with high-risk proliferative diabetic retinopathy (HRPDR). Furthermore, we misled to compare the session number performed and the side effects produced by the two techniques. METHODS: Sixty-five eyes with HRPDR of 50 consecutive patients were enrolled in a prospective randomized controlled trial. In eyes selected for light PRP, a very light biomicroscopic effect on the retina was obtained for each spot. In eyes assigned to classic PRP, each spot produced a white-yellow biomicroscopic effect. Mean follow-up was 22.4 months +/- 9.7 in the light PRP and 21.6 months +/- 9.3 in the classic PRP group (p = 0.727). RESULTS: The initial mean logMAR visual acuity (VA) in the light PRP group was 0.12 +/- 0.13 and in the classic PRP group 0.14 +/- 0.15 (p = 0.493). The final mean VA in the former was 0.18 +/- 0.25, and in the latter 0.27 +/- 0.30 (p = 0.231). Median power was 235mW (100-540mW) for light and 420mW (200-950mW) for classic PRP (p < 0.001). Regression of HRPDR at the end of the follow-up was obtained in 30/31 eyes (97%) treated with classic PRP and in 31/34 eyes (91%) treated with light PRP (p = 0.615). The total mean session number was 7.4 +/- 2.4 for light and 9.9 +/- 2.2 for the classic PRP group (p < 0.001). Complications were more frequent in the classic PRP group. CONCLUSIONS: The efficacy of Light PRP is similar to that of classic Light PRP in eyes with HRPDR. Light PRP is associated with fewer complications and allows the reduction of the number of treatment sessions.

Real time fixation point monitoring system for photocoagulation of juxtafoveal neovascularisation.

BACKGROUND/AIMS: A new real time monitoring system has been developed to locate the fixation point during juxtafoveal laser photocoagulation. METHOD: The red diode laser beam is combined coaxially with the illumination beam to image a cross in the focal plane of the slit lamp, which allows projection of a red cross onto the patient's fundus. 27 patients with juxtafoveal choroidal neovascularisation were treated by photocoagulation using this system. RESULTS: 13 (48%) patients whose visual acuity ranged from 20/200 to 20/40 answered that it was easier to keep the focus on the cross target image than on the aiming beam. The patient maintained stable fixation throughout the treatment. The laser treatment was completed without foveal damage near the fixation point in all patients. CONCLUSION: The real time fixation monitoring system should allow surgeons to treat juxtafoveal lesions with laser photocoagulation more safely and accurately.

Argon beam coagulation systems.

We evaluated the two argon-enhanced coagulation (AEC) systems currently on the market from two different manufacturers, basing our ratings primarily on performance and safety and considering the clinical perspectives gained from discussions with surgeons who use these units. We rated both units Acceptable. Because one unit has characteristics that provide a potential safety advantage (i.e., it produces lower gas pressure at the tissue and limits certain gas flow/power combinations), we ranked it slightly higher than the other unit. However, sufficient laboratory and clinical studies must still be carried out to assess the risk of gas embolism with these and future systems.

Fotocoagulacion laser verde en edemas maculares: un estudio retrospectivo: Fundacion Oftalmologica Colombiana Medellin 1987-1988 / Photocoagulation with laser in macular edema: a retrospective study: Fundacion Oftalmologica Colombiana Medellin 1987-1988

Se evaluaron las historias de 37 pacientes (50) ojos, con diagnostico de edema macular tratados con Laser de Argon en la Fundacion Oftalmologica Colombiana, entre agosto de 1987 y agosto de 1988. El objetivo principal del estudio fue determinar la eficacia del tratamiento en dicha institucion y establecer unos patrones basico de su aplicación. Se realizo el tratamiento con Laser verde Argon, de acuerdo con el patron angiografico y/o clínico por medio de tres patrones: "grid: o rejilla (62%), focal (22%) y en "C" (16%) rodeando el area comprometida y evitando el haz papilomacular. En algunos casos se hizo combinacion de estos metodos. Hubo mejoria de la agudeza visual, determinada en una cartilla de optotipos de Snellen, en 25 ojos (50%), no hubo variación en 20 ojos (40%), y empeoro en 5 ojos (10%). Haciendo un analisis estadistico para datos independientes apareados (prueba de T pareada), se encontro significancia estadistica a un nivel del 99% (p= 0.000795), con una confiabilidad del 70%. No hubo una correlación definida entre el tipo de patron del tratamiento y la mejoria en la agudeza visual, pero si con el tipo de patologia de base del edema macular

[Classification of diabetic retinopathy and application standard of photocoagulation].

It has been confirmed in some prefectures in Japan that severe diabetic retinopathy became the leading cause of blindness. The authors described classification of diabetic retinopathy and discussed that in order to prevent blindness due to diabetic retinopathy, it was absolutely necessary to place fundus examination in the management system of diabetes and also to include photocoagulation therapy in the management system of diabetic retinopathy. Application of fundus examination in the management system of diabetes was described correspondingly in cases with or without retinopathy and in cases of each type of diabetic retinopathy. Indication of photocoagulation for diabetic retinopathy was discussed, according to types of the retinopathy, such as maculopathy, preproliferative retinopathy or early stage of proliferative retinopathy. Standard technique of photocoagulation in each type of the retinopathy was discussed. Particularly it was stressed that the panretinal photocoagulation should not be performed in a single session, but should be performed separately in four or five sessions at one week interval.

Neodymium: YAG laser specifications for safe intravesical therapy.

The depth of penetration of a laser beam is a critical factor in determining the therapeutic potential and risks of treatment. Variable parameters of laser energy were applied endoscopically in dog bladders. Although there was a clear trend toward greater depth of necrosis with increased energy, marked variability occurred within each set of energy specifications. Full thickness injuries with penetration depths up to five mm. were observed in some animals at all energy levels above 120 joules. A number of variables affect the penetration depth of a Nd:YAG laser, some of which are difficult to control with precision in an endoscopic setting.

La fotocoagulacion panretiniana con laser de argon en la retinopatia diabetica proliferativa / The panretinal photocoagulation with argon laser in the proliferative diabetic retinopathy

El objetivo del presente trabajo es el de presentar el resutlado de la regresion clinica de la neovascularizacion en 114 ojos afectado de retinopatia diabetica proliferativa, luego del tratamiento con laser azul-verde de argon, mediante la fotocoagulacion panretiniana. La experiencia se desarrollo en 114 ojos de 60 pacientes diabeticos tipos I y II con un tiempo promedio de evolucion de esta enfermedad de 14 anos con edades comprendidas entre 17 y 78 anos y distribuidos por sexos asi: 36 hombres y 24 mujeres. Se hallaron alteraciones oculares asociadas, tales como catarata, glaucoma y rubeosis del iris. Se comentan los factores de riesgo hallados, siguiendo la clasificacion del Diabetic Retinopaty Study Group. La tecnica de la fotocoagulacion panretiniana empleada en esta serie, fue la suegerida por el mismo DRS, igual que la valoracion de los resultados, los cuales, en un reducido numero de pacientes, no fueron exitosos, observandose algunas complicaciones posteriores al procedimiento.

The role of fluorescein angiography in national collaborative studies.

Over the past 20 years, fluorescein angiography has demonstrated its value in the diagnosis and management of most diseases of the retinal vessels and choroidal vessels, including diabetic retinopathy, aging macular degeneration, and venous occlusive disorders. Fluorescein angiography has become so important for diagnostic purposes and for laser management that it has become a standard technique in the authors' most carefully performed clinical research studies such as randomized clinical trials. These clinical trials demand fluorescein angiography not only for diagnosis and eligibility of patients, but also to document the adequacy of laser photocoagulation. The use of fluorescein angiography has encouraged the development of newer photographic techniques and has encouraged a commendable level of expertise among photographers. Experience with fluorescein angiography in clinical trials has led to the development of general guidelines for the use of angiography for the management of patients outside the confines of a clinical trial; we emphasize the importance of recent angiography as a general guideline for all patients with macular edema or choroidal neovascularization before consideration of laser photocoagulation.

Ocular histoplasmosis syndrome.

The Macular Photocoagulation Study (MPS) is a multi-center clinical trial supported by the National Eye Institute whose purpose is to assess argon laser photocoagulation as a treatment for choroidal neovascular membranes (NVMs) that do not involve the fovea. The MPS documented that in patients with ocular histoplasmosis syndrome argon laser photocoagulation in comparison with no treatment can reduce the risk of severe visual loss from 46 to 13% in the first two years. Accordingly, patients with ocular histoplasmosis and NVMs outside the fovea are advised to undergo prompt treatment with argon laser photocoagulation.

Evaluation of medical data: role of clinical trials.

Over the centuries, methods have been developed to evaluate diseases and their treatments. One systematic method is the case series, in which groups of patients are followed over time to estimate the likelihood of various disease outcomes, either with or without treatment. A more efficient method for assessing treatment effectiveness is the clinical trial. Both methods have been used for evaluating current treatments of macular diseases. the combination of case series and clinical trials has been used to advantage for many of these diseases. However, when one wants to be certain that a treatment is effective, there is no substitute for the clinical trial.

Clinical trials versus intuition in evaluating the results of laser photocoagulation.

Clinical trials are often used to evaluate the efficacy of a given treatment. The results of clinical trials however do not always agree with a clinician's experience or intuition. The merits and demerits of Clinical Trials versus Intuition are discussed by using the laser photocoagulation trials of Proliferative Diabetic Retinopathy, Central serous retinopathy, Branch Vein Occlusion (treatment for macular oedema), Senile Macular Degeneration, and Pigment Epithelial Detachment. A model based on Intuition is used to explain the discrepancy between the results of the British and American trials of Branch Vein Occlusion and Senile Macular Degeneration. Proposals on the presentation of Clinical Trials and the place of Intuition are made.