Cyclodestruction and cyclophotocoagulation: Where are we?

Cyclodestruction is a technique reserved for glaucomas not controlled with medical and surgical treatment and poor visual potential. During the last century, new cyclodestructive techniques were developed, including cyclophotocoagulation, and the use of continuous-wave diode laser transescleral cyclophotocoagulation (CW-TS-CPC) has become widespread. In recent decades, micropulse diode laser transescleral cyclophotocoagulation (MP-TS-CPC) was introduced. We review the cyclodestruction techniques since their origins and these two techniques of cyclophotocoagulation, which are currently the most widely used: how they are performed, their mechanisms of action and their effectiveness and efficacy. We also review the comparison between them and with other techniques.

Congenital retinal macrovessels: Case presentation.

We present an uncommon case of a unilateral congenital retinal macrovessel documented with retinography, perimetry, fluorescein angiography and macular optical coherence tomography. In the case presented the macrovessel crossed the horizontal meridian, between macula and optic disk. A literature review has been performed on congenital retinal macrovessels, possible structural and visual alterations they may cause and their association with other pathologies.

Mapping the thickness changes on retinal layers segmented by spectral-domain optical coherence tomography using the posterior pole program in glaucoma. / Mapeo de los cambios de grosor en el glaucoma de las capas retinianas maculares segmentadas usando el programa de polo posterior de la tomografía de coherencia óptica de dominio espectral.

OBJECTIVES: To evaluate changes in retinal layers of the macula (mRLs) using OCT posterior pole program (PPP) in primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 128 patients with POAG and 103 healthy controls who had PPP maps (macular grid 8×8) drawn by SD-OCT. Only one eye per patient was studied. The 9 mRLs were automatically segmented by prototype software, obtaining: a macular retinal nerve fibre layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform+nuclear layer, photoreceptor layer, retinal pigment epithelium (RPE), outer retina and RPE+outer retina. Thickness values were obtained on 64 cells of the grid for each mRL, and mean thickness of superior and inferior hemispheres were calculated. Comparisons of mean thickness of these hemispheres and thickness of each cell between groups were determined. Differences in the cell by cell comparisons were represented quantitatively by heat maps for each mRL. RESULTS: Photoreceptors and RPE were found in POAG group when comparing thickness of hemispheres, thinning of mRNFL, GCL, IPL, and thickening of INL. Heat maps showed symmetrical thinning patters between superior and inferior hemispheres in inner retinal layers (except for INL) and asymmetrical thickening patters in outer retinal layers in GPAA group. CONCLUSIONS: There are thickness changes in all mRLs in POAG, when studied by PPP. Thinning of inner layers (except for INL), and thickening of outer layers in POAG show different symmetry patterns in relation to horizontal meridian.

Lifestyles guide and glaucoma (i). Sports and activities. / Guía de estilos de vida y glaucoma (i). Deporte y actividades.

PURPOSES: The increase in quality and life expectancy, often leads to many patients asking the glaucoma specialist whether some sports, activities or hobbies would affect their illness. The aim of this article is to establish guidelines for patients, based on the scientific evidence of published papers. METHODS: Review of all published articles on glaucoma and sports or other activities. The papers were classified according to the level of scientific evidence based on the Oxford Centre for Evidence-Based Medicine classification. RESULTS: Aerobic sports are beneficial for the patient. Yoga indoor sports or relaxation techniques should be avoided if Valsalva manoeuvres are performed or the head is placed very low. Also, the patients must avoid sudden changes in height. Intense heat does not seem to lead to progression of glaucoma, but intense cold can affect patients with vascular dysregulation. Activities using the near vision slightly reduce the intraocular pressure. The use of wind instruments may raise intraocular pressure, depending on the technique used. CONCLUSIONS: Certain sports and activities may have an influence on the onset or progression of glaucoma. Glaucoma specialists should have adequate information about the scientific evidence in the publications, in order to properly advise the patients.

Lifestyles guide and glaucoma (II). Diet, supplements, drugs, sleep, pregnancy, and systemic hypertension. / Guía de estilos de vida y glaucoma (II). Dieta, suplementos, drogas, sueño, embarazo e hipertensión arterial.

PURPOSE: To establish evidence based guidelines to advise patients on the relationship between habits, diet, certain circumstances, diseases and glaucoma. METHODS: Review of all published articles on glaucoma and sports or other activities. The papers were classified according to the level of scientific evidence based on the Oxford Centre for Evidence-based Medicine classification. RESULTS: The evidence on the relationship between diet or supplements and the incidence or progression of glaucoma is insufficient to make a general recommendation for glaucoma patients. Although some studies on normal tension glaucoma suggest that Gingko biloba could reduce glaucoma progression, the results do not allow a general recommendation for all these patients. Similarly, the evidence on the usefulness of vitamin supplements is not conclusive. The studies on smoking do not clearly demonstrate the relationship between this habit and incidence of glaucoma. Marihuana is not a useful treatment for glaucoma. Although the results on the relationship between sleep apnoea and glaucoma are heterogeneous, it is recommended that patients with moderate to intense apnoea are tested for glaucoma. Pregnancy does not influence the course of the disease, but several hypotensive drugs may be harmful for the foetus. Nocturnal systemic hypotension is a risk factor for glaucoma progression. CONCLUSIONS: Certain habits, circumstances, or diseases may have an influence on the onset or progression of glaucoma. It is important to have adequate information about the scientific evidence in the publications in order to properly advise patients.

Difficulties in the management of retinal capillary haemangiomas associated with von Hippel Lindau disease. / Dificultades en el manejo de los hemangiomas capilares retinianos asociados a enfermedad de von Hippel-Lindau.

CLINICAL CASE: A 29-year-old female with bilateral retinal capillary haemangiomas (RCH). A genetic analysis was carried out due to the suspicion of von Hippel-Lindau (VHL) disease, with negative results on 2occasions. There was progression of the RCH in the left eye, leading to a macular epiretinal membrane. The patient was treated with laser, intravitreal ranibizumab, and vitrectomy. Finally, a third genetic test detected a de novo mutation in the VHL gene, and led to the genetic diagnosis. DISCUSSION: VHL syndrome causes a complex ocular disease with a difficult diagnosis that requires early treatment of the RCH in order to modify its visual prognosis.

Guidelines for treatment of chronic primary angle-closure glaucoma.

OBJECTIVE: To present a clinical practice guideline update on the medical, laser, and surgical treatment of primary angle closure glaucoma (PACG) in adults. METHODS: Following the formulation of key questions using the PICO scheme (Patient/Problem, Intervention, Comparison, Outcome), a systematic review was performed on the literature published to date, including international clinical practice guidelines. The AMSTAR and Risk of Bias tools were used for evaluating the quality of the information. The level of evidence and grade of recommendation was established following the Scottish Intercollegiate Guidelines Network (SIGN) system. RESULTS: Following the above methodology, recommendations of medical, laser and surgical treatment in adult PACG and levels of evidence are presented. CONCLUSIONS: Although the level of scientific evidence for many of the questions raised is not very high, a review is presented on updated treatment recommendations for adult PACG. Among the limitations for the implementation of these recommendations is that most studies have been conducted in Asian populations, and that the effectiveness is measured almost exclusively in terms of reducing intraocular pressure, and does not include visual function, quality of life or cost-effectiveness parameters.

[Fungal keratitis caused by Colletotrichum spp. A presentation of case]. / Queratitis fúngica por Colletotrichum spp. A propósito de un caso.

CASE REPORT: A 23 years old male with an unremarkable past medical history suffered an injury with a branch of a lemon tree in the right eye two days prior to presentation. The slit-lamp examination showed a central corneal erosion with a white tree-shaped stromal infiltrate and Tyndall +/++ in anterior chamber. Cultivation of corneal scraping was positive for Colletotrichum spp. The patient responded favourably to topical amphotericin. DISCUSSION: Colletotrichum spp. is an uncommon cause of keratitis, usually secondary to corneal erosion caused by plant material and should be included in the differential diagnosis of fungal keratitis.

Number and spatial distribution of intrinsically photosensitive retinal ganglion cells in the adult albino rat.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light and are responsible of the synchronization of the circadian rhythm with the photic stimulus and for the pupillary light reflex. To quantify the total population of rat-ipRGCs and to assess their spatial distribution we have developed an automated routine and used neighbour maps. Moreover, in all analysed retinas we have studied the general population of RGCs - identified by their Brn3a expression - and the population of ipRGCs - identified by melanopsin immunodetection - thus allowing the co-analysis of their topography. Our results show that the total mean number ± standard deviation of ipRGCs in the albino rat is 2047 ± 309. Their distribution in the retina seems to be complementary to that of Brn3a(+)RGCs, being denser in the periphery, especially in the superior retina where their highest densities are found in the temporal quadrant, above the visual streak. In addition, by tracing the retinas from both superior colliculi, we have also determined that 90.62% of the ipRGC project to these central targets.

Anatomical and functional damage in experimental glaucoma.

Glaucoma is a progressive neurodegenerative disease caused by retinal ganglion cell (RGC) loss. One important risk factor for glaucoma is elevated intraocular pressure and thus many animal models are based on spontaneous or induced ocular hypertension (OHT). Using these models it has been shown that RGCs initially suffer an impairment of the active axonal transport that progresses to a lack of passive diffusion along the axon. This axonal damage eventually causes the death of the parent RGCs in pie-shaped sectors of the retina, but there is also diffuse RGC loss, without involving displaced amacrine cells. Recent data show that OHT results in a protracted insult to the inner and outer retina that causes functional alterations and ultimately, degeneration and death of cones.

Axotomy-induced retinal ganglion cell death in adult mice: quantitative and topographic time course analyses.

The fate of retinal ganglion cells after optic nerve injury has been thoroughly described in rat, but not in mice, despite the fact that this species is amply used as a model to study different experimental paradigms that affect retinal ganglion cell population. Here we have analyzed, quantitatively and topographically, the course of mice retinal ganglion cells loss induced by intraorbital nerve transection. To do this, we have doubly identified retinal ganglion cells in all retinas by tracing them from their main retinorecipient area, the superior colliculi, and by their expression of BRN3A (product of Pou4f1 gene). In rat, this transcription factor is expressed by a majority of retinal ganglion cells; however in mice it is not known how many out of the whole population of these neurons express it. Thus, in this work we have assessed, as well, the total population of BRN3A positive retinal ganglion cells. These were automatically quantified in all whole-mounted retinas using a newly developed routine. In control retinas, traced-retinal ganglion cells were automatically quantified, using the previously reported method (Salinas-Navarro et al., 2009b). After optic nerve injury, though, traced-retinal ganglion cells had to be manually quantified by retinal sampling and their total population was afterwards inferred. In naïve whole-mounts, the mean (±standard deviation) total number of traced-retinal ganglion cells was 40,437(±3196) and of BRN3A positive ones was 34,697(±1821). Retinal ganglion cell loss was first significant for both markers 5 days post-axotomy and by day 21, the last time point analyzed, only 15% or 12% of traced or BRN3A positive retinal ganglion cells respectively, survived. Isodensity maps showed that, in control retinas, BRN3A and traced-retinal ganglion cells were distributed similarly, being densest in the dorsal retina along the naso-temporal axis. After axotomy the progressive loss of BRN3A positive retinal ganglion cells was diffuse and affected the entire retina. In conclusion, this is the first study assessing the values, in terms of total number and density, of the retinal ganglion cells surviving axotomy from 2 till 21 days post-lesion. Besides, we have demonstrated that BRN3A is expressed by 85.6% of the total retinal ganglion cell population, and because BRN3A positive retinal ganglion cells show the same spatial distribution and temporal course of degeneration than traced ones, BRN3A is a reliable marker to identify, quantify and assess, ex-vivo, retinal ganglion cell loss in this species.

Retinal ganglion cell population in adult albino and pigmented mice: a computerized analysis of the entire population and its spatial distribution.

UNLABELLED: In adult Swiss albino and C57 pigmented mice, RGCs were identified with a retrogradely transported neuronal tracer applied to both optic nerves (ON) or superior colliculi (SCi). After histological processing, the retinas were prepared as whole-mounts, examined and photographed under a fluorescence microscope equipped with a motorized stage controlled by a commercial computer image analysis system: Image-Pro Plus((R)) (IPP). Retinas were imaged as a stack of 24-bit color images (140 frames per retina) using IPP with the Scope-Pro plug-in 5.0 and the images montaged to create a high-resolution composite of the retinal whole-mount when required. Single images were also processed by specific macros written in IPP that apply a sequence of filters and transformations in order to separate individual cells for automatic counting. Cell counts were later transferred to a spreadsheet for statistical analysis and used to generate a RGC density map for each retina. RESULTS: The mean total numbers of RGCs labeled from the ON, in Swiss (49,493+/-3936; n=18) or C57 mice (42,658+/-1540; n=10) were slightly higher than the mean numbers of RGCs labeled from the SCi, in Swiss (48,733+/-3954; n=43) or C57 mice (41,192+/-2821; n=42), respectively. RGCs were distributed throughout the retina and density maps revealed a horizontal region in the superior retina near the optic disk with highest RGC densities. In conclusion, the population of mice RGCs may be counted automatically with a level of confidence comparable to manual counts. The distribution of RGCs adopts a form of regional specialization that resembles a horizontal visual streak.

A computerized analysis of the entire retinal ganglion cell population and its spatial distribution in adult rats.

In adult albino (SD) and pigmented (PVG) rats the entire population of retinal ganglion cells (RGCs) was quantified and their spatial distribution analyzed using a computerized technique. RGCs were back-labelled from the optic nerves (ON) or the superior colliculi (SCi) with Fluorogold (FG). Numbers of RGCs labelled from the ON [SD: 82,818+/-3,949, n=27; PVG: 89,241+/-3,576, n=6) were comparable to those labelled from the SCi [SD: 81,486+/-4,340, n=37; PVG: 87,229+/-3,199; n=59]. Detailed methodology to provide cell density information at small scales demonstrated the presence of a horizontal region in the dorsal retina with highest densities, resembling a visual streak.

High resolution imaging of fluorescein patterns in RCS rat retinae and their direct correlation with histology.

To assess the progressive changes in the retinal vascular bed of dystrophic and non-dystrophic Royal College of Surgeons (RCS) rats, retinae, were visualised correlating in vivo fundus fluorescein angiography (FA) with histology. FA was performed in rats aged 5 weeks to 2 years, using a Zeiss confocal scanning laser ophthalmoscope (cSLO). After the final imaging session, a subset of retinae were prepared for flat-mount histology and the vascular bed was visualised using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining. While non-dystrophic rat retinae showed no substantive changes in vascular patterns with age and no demonstrable fluorescein leakage up to at least 1 year, dystrophic rat retinae showed abnormal vascular formations, demonstrable on FA and NADPH-d staining, which could be correlated in single retinae. Hyperfluorescent spots and late angiographic leakage were evident beginning at 10 weeks and progressed in severity with time: they were coincident in distribution with abnormal histological vascular complexes. The ability to monitor the same retina serially makes this approach a valuable tool for studying the dynamics of vascular change in the diseased retina, not only during the course of degeneration but also when assessing efficacy of potential therapeutic approaches.

Evolving neurovascular relationships in the RCS rat with age.

PURPOSE: To examine the course of development of vascular disorders in the Royal College of Surgeons (RCS) rat and how these may lead to retinal ganglion cell loss. METHODS: Whole-mount retinae from RCS rats were first stained for neurofilament protein and then for NADPH-diaphorase staining. A separate group of RCS rats was injected with Type II Peroxidase and the retinae were subsequently processed for peroxidase histochemistry. RESULTS: The first changes in the deep vascular plexus occur as the photoreceptor layer is lost and it comes into close proximity to the retinal pigment epithelial (RPE) cell layer. RPE cells migrate onto retinal vessels, and at such locations vascular complex develop. These are first found ventral to the optic nerve head and then gradually progress over most of the retina. The inner retinal vessels that supply the complexes cross the optic nerve fiber layer and appear to be under tension. They ligate axons, which leads to retinal ganglion cell loss. CONCLUSIONS: These observations show vascular changes can have secondary repercussions for neurons distant from the primary lesion.

Neuroprotective effects of brimonidine against transient ischemia-induced retinal ganglion cell death: a dose response in vivo study.

The purpose of this study was to investigate the dose-response effects of topically administered brimonidine (BMD) on retinal ganglion cell (RGC) survival, short and long periods of time after transient retinal ischemia. In adult Sprague-Dawley rats, RGCs were retrogradely labeled with the fluorescent tracer fluorogold (FG) applied to both superior colliculi. Seven days later, the left ophthalmic vessels were ligated for 90 min. One hr prior to retinal ischemia, two 5 microl drops of saline alone or saline containing 0.0001, 0.001, 0.01 or 0.1% BMD were instilled on the left eye. Rats were processed 7, 14 or 21 days later and densities of surviving RGCs were estimated by counting FG-labeled RGCs in 12 standard regions of each retina. The following have been found. (1) Seven days after 90 min of transient ischemia there is loss of approximately 46% of the RGC population. (2) topical pre-treatment with BMD prevents ischemia-induced RGC death in a dose-dependent manner. Administration of 0.0001% BMD resulted in the loss of approximately 37% of the RGC population and had no significant neuroprotective effects. Administration of higher concentrations of BMD (0.001 or 0.01%) resulted in the survival of 76 or 90%, respectively, of the RGC population, and 0.1% BMD fully prevented RGC death in the first 7 days after ischemia. (3) Between 7 and 21 days after ischemia there was an additional slow cell loss of approximately 25% of the RGC population. Pre-treatment with 0.1% BMD also reduced significantly this slow cell death. These results indicate that the neuroprotective effects of BMD, when administered topically, are dose-dependent and that the 0.1% concentration achieves optimal neuroprotective effects against the early loss of RGCs. Furthermore, this concentration is also effective to diminish the protracted loss of RGCs that occurs with time after transient ischemia.