Ultra-widefield fundus fluorescein angiography in the diagnosis and management of retinal vasculitis.

PurposeTo quantify the additional information provided by ultra-widefield fluorescein angiography, compared with 7-field standard imaging, in patients with retinal vasculitis (RV).Patients and methodsRetrospective case series of 106 patients.ResultsRetinal vascular pathology was identified by UWF FFA, but not by standard ETDRS 7-field area, in 62 patients (58.5%) and in 79 eyes (43.4%). The pathology included active RV (47 eyes, 25.8% of eyes); retinal ischaemia, or infarction (53 eyes, 29.1%); and retinal neovascularization (7 eyes, 3.8%). A change to management was made in 36 patients (34%). Of these, 21 (20% of all patients undergoing angiography) were made after the identification of retinal vascular pathology, which was found only on UWF FFA, outside the ETDRS area.ConclusionUltra-widefield fluorescein angiography has clear advantages over standard multi-field imaging. It is currently the standard method of assessment for RV in this centre.

Electronic retinal implants and artificial vision: journey and present.

Retinitis pigmentosa and age-related macular degeneration are two significant causes of severe visual dysfunction. In both, the retinal photoreceptors degenerate, preventing successful conversion of light into electrical energy that is interpreted in the visual cortex as visual function. Artificial vision or visual function began over two centuries ago with the idea of creating artificial light pulses, or phosphenes, through cortical stimulation. The pursuit is now on to improve artificial visual function. Two retinal implants appear the most likely to succeed in the future having undergone multicentre human trials: the Argus II electronic epiretinal device (Second Sight Medical Products, CA, USA) and Alpha-IMS electronic subretinal device (Retina Implant AG, Germany). The trial results to date are encouraging with visual improvement and acceptable safety profiles reported for both devices. At present, the visual function generated by either device does not offer high enough resolution or acuity for a patient to regain a fully functional life. Despite this, both devices not only have the potential, but have actually improved the vision-related quality of life in a significant number of patients implanted. With this in mind, the economic argument is clear. Provided device-life is long enough, its cost should be acceptable for the obtained improvement in the quality of life. The aim of this Review Article is to assist those readers that may be considering offering any of these devices as a treatment for blindness in Retinitis Pigmentosa.

Pascal panretinal laser ablation and regression analysis in proliferative diabetic retinopathy: Manchester Pascal Study Report 4.

AIMS: To quantify the 20-ms Pattern Scan Laser (Pascal) panretinal laser photocoagulation (PRP) ablation dosage required for regression of proliferative diabetic retinopathy (PDR), and to explore factors related to long-term regression. METHODS: We retrospectively studied a cohort of patients who participated in a randomised clinical trial, the Manchester Pascal Study. In all, 36 eyes of 22 patients were investigated over a follow-up period of 18 months. Primary outcome measures included visual acuity (VA) and complete PDR regression. Secondary outcomes included laser burn dosimetry, calculation of retinal PRP ablation areas, and effect of patient-related factors on disease regression. A PDR subgroup analysis was undertaken to assess all factors related to PDR regression according to disease severity. RESULTS: There were no significant changes in logMAR VA for any group over time. In total, 10 eyes (28%) regressed after a single PRP. Following top-up PRP treatment, regression rates varied according to severity: 75% for mild PDR (n=6), 67% for moderate PDR (n=14), and 43% in severe PDR (n=3). To achieve complete disease regression, mild PDR required a mean of 2187 PRP burns and 264 mm(2) ablation area, moderate PDR required 3998 PRP burns and area 456 mm(2), and severe PDR needed 6924 PRP laser burns (836 mm(2); P<0.05). CONCLUSIONS: Multiple 20-ms PRP treatments applied over time does not adversely affect visual outcomes, with favourable PDR regression rates and minimal laser burn expansion over 18 months. The average laser dosimetry and retinal ablation areas to achieve complete regression increased significantly with worsening PDR.

Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task.

BACKGROUND/AIMS: To determine to what extent subjects implanted with the Argus II retinal prosthesis can improve performance compared with residual native vision in a spatial-motor task. METHODS: High-contrast square stimuli (5.85 cm sides) were displayed in random locations on a 19″ (48.3 cm) touch screen monitor located 12″ (30.5 cm) in front of the subject. Subjects were instructed to locate and touch the square centre with the system on and then off (40 trials each). The coordinates of the square centre and location touched were recorded. RESULTS: Ninety-six percent (26/27) of subjects showed a significant improvement in accuracy and 93% (25/27) show a significant improvement in repeatability with the system on compared with off (p<0.05, Student t test). A group of five subjects that had both accuracy and repeatability values <250 pixels (7.4 cm) with the system off (ie, using only their residual vision) was significantly more accurate and repeatable than the remainder of the cohort (p<0.01). Of this group, four subjects showed a significant improvement in both accuracy and repeatability with the system on. CONCLUSION: In a study on the largest cohort of visual prosthesis recipients to date, we found that artificial vision augments information from existing vision in a spatial-motor task. Clinical trials registry no NCT00407602.

High-resolution hyperspectral imaging of the retina with a modified fundus camera.

PURPOSE: to examine the practical feasibility of developing a hyperspectral camera from a Zeiss fundus camera and to illustrate its use in imaging diabetic retinopathy and glaucoma patients. METHODS: the original light source of the camera was replaced with an external lamp filtered by a fast tunable liquid-crystal filter. The filtered light was then brought into the camera through an optical fiber. The original film camera was replaced by a digital camera. Images were obtained in normals and patients (primary open angle glaucoma, diabetic retinopathy) recruited at the Manchester Royal Eye Hospital. RESULTS: a series of eight images were captured across 495- to 720-nm wavelengths, and recording time was less than 1.6s. The light level at the cornea was below the ANSI limits, and patients judged the measurement to be very comfortable. Images were of high quality and were used to generate a pixel-to-pixel oxygenation map of the optic nerve head. Frame alignment is necessary for frame-to-frame comparison but can be achieved through simple methods. CONCLUSIONS: we have developed a hyperspectral camera with high spatial and spectral resolution across the whole visible spectrum that can be adapted from a standard fundus camera. The hyperspectral technique allows wavelength-specific visualization of retinal lesions that may be subvisible using a white light source camera. This hyperspectral technique may facilitate localization of retinal and disc pathology and consequently facilitate the diagnosis and management of retinal disease.

Pain responses of Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation: Manchester Pascal Study, MAPASS report 2.

AIMS: To evaluate pain responses following Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation (PRP). METHODS: Single-centre randomised clinical trial. 40 eyes of 24 patients with treatment-naive proliferative diabetic retinopathy randomised to 20 and 100 ms PRP under topical 0.4% oxybuprocaine. A masked grader used a pain questionnaire within 1 h (numerical pain score (NPS)) and 1 month after treatment (numerical headache score (NHS)). Primary outcome measure was NPS immediately post-PRP. Secondary outcome measures were mean NHS scores and levels of photophobia reported within 4 weeks of primary PRP. RESULTS: Mean laser fluence was significantly lower using 20 ms PRP (4.8 J/cm²) compared to 100 ms PRP (11.8 J/cm²); p < 0.001). Mean NPS scores for treatment were 2.4 (2.3) (mild) for 20 ms PRP group compared to 4.9 (3.3) (moderate) in 100 ms PRP group-a significant difference (95% CI 4.3 to 0.68; p = 0.006). Mean NHS score within 1 month was 1.5 (2.7) in 20 ms PRP group compared to 3.2 (3.5) in the 100 ms PRP group (p < 0.05). The median duration of photophobia after 20 ms PRP was 3 h, and significantly less compared to 100 ms PRP after which 72 h of photophobia was reported (p < 0.001). CONCLUSIONS: Multi-spot 20 ms PRP was associated with significantly lower levels of anxiety, headache, pain and photophobia compared to 100 ms single-spot PRP treatment. Possible reasons include lower fluence, shorter-pulse duration, and spatial summation of laser nociception with multi-spot Pascal technique.

Effects of conventional argon panretinal laser photocoagulation on retinal nerve fibre layer and driving visual fields in diabetic retinopathy.

AIMS: To determine the effects of argon green panretinal laser photocoagulation on retinal nerve fibre layer thickness, threshold visual fields, and Estermann full-binocular visual fields over time in diabetic retinopathy. METHOD: Prospective, pilot clinical study. Time-domain optical coherence tomography (TD-OCT) of the optic nerve head and 24-2 SITA-Fast Humphrey/Estermann visual fields (HVF, EVFs) recorded at baseline, 10 weeks, and 6 months post laser. Quantitative field analysis of central 10 degrees, 24 degrees, and binocular visual fields. RESULTS: A total of 10 eye samples were subjected to uncomplicated multiple-session 100 ms panretinal laser using 2000 burns, 300-microm spot, and mean power of 136 mW (SD+/-39.3). TD-OCT detected and quantified an increase in mean retinal nerve fibre layer thickness at 10 weeks (+8 microm; P<0.05) and progressive thinning at 6 months (-4 microm; P<0.05) compared with baseline. Mean threshold sensitivities, and 10 degrees and 24 degrees HVF improved at both time points in the majority (9 of 10 and 8 of 10) of patients. EVFs showed no significant change with treatment. CONCLUSIONS: This pilot study shows that conventional argon laser panretinal photocoagulation may increase the retinal nerve fibre layer thickness in the short term, presumably related to laser-induced axonal injury, with progressive thinning of nerve fibre layer over the long term. The 10 degrees and 24 degrees visual fields improved significantly after laser with no adverse effects on the UK standard driving fields.

Fundus autofluorescence and Fourier-domain optical coherence tomography imaging of 10 and 20 millisecond Pascal retinal photocoagulation treatment.

AIM: To report the evolution of pattern scanning laser (Pascal) photocoagulation burns in the treatment of diabetic retinopathy, using Fourier-domain optical coherence tomography (FD-OCT) and fundus autofluorescence (AF), and to evaluate these characteristics with clinically visible alterations in outer retina (OR) and retinal pigment epithelium (RPE). METHODS: Standard red-free and colour fundus photography (FP), FD-OCT, and fundus camera-based AF were performed in 17 eyes of 11 patients following macular and panretinal photocoagulation (PRP). RESULTS: One hour following Pascal application, visibility of threshold burns on FP was incomplete. AF enabled visualisation of complete treatment arrays at 1 h, with hypoautofluorescence at sites of each laser burn. AF signals accurately correlated with localised increased optical reflectivity within the outer retina on FD-OCT. AF signals became hyperautofluorescent at 1 week, and corresponded on FD-OCT to defects at the junction of the inner and outer segments of the photoreceptors (JI/OSP) and upper surface of RPE. A 10 ms macular laser pulse produced a localised defect at the level of JI/OSP and RPE. Macular and 20 ms PRP burns did not enlarge at 1 year's and 18 months' follow-up respectively. CONCLUSIONS: We report the in vivo spatial localisation and clinical correlation of medium-pulse Pascal photocoagulation burns within outer retina and RPE, using high-resolution FD-OCT and AF. Ophthalmoscopically invisible and threshold Pascal burns may be accurately localised and mapped by AF and FD-OCT, with monitoring over time.

Initial experience with the Pascal photocoagulator: a pilot study of 75 procedures.

BACKGROUND: The Pascal is a semiautomated photocoagulator that delivers a pattern array of multiple burns in a rapid predetermined sequence with a single foot pedal depression. Each burn is reduced to 10 or 20 ms to achieve this. The authors report their early experience with this system. METHODS: 75 procedures done in 60 patients divided into four groups-group A, patients undergoing panretinal photocoagulation (PRP); group B, patients undergoing focal or modified grid macular laser; group C, patients undergoing macular grid and group D, patients undergoing retinopexy-were retrospectively studied. RESULTS: 31/34 procedures in group A, 24/26 procedures in group B, 5/7 procedures in group C and all eight patients in group D had successful outcomes. Significantly higher powers were required with the Pascal than with conventional laser (p<0.001) in eyes that underwent PRP and focal/modified grid macular treatment with both systems. Single session PRP was successfully performed in five patients, and five were successfully treated with a macular grid using pattern arrays only. No adverse events were noted. CONCLUSION: Although the shorter pulse duration of the Pascal necessitates the use of a higher power, it is not associated with adverse effects. The results here suggest that the Pascal photocoagulator is safe and effective, and offer several potential advantages related to the brief exposure time.

Optical coherence tomography in photodynamic therapy for subfoveal choroidal neovascularisation secondary to age related macular degeneration: a cross sectional study.

AIMS: To introduce new terminology and validate its reliability for the analysis of optical coherence tomography (OCT) scans, compare clinical detection of cystoid macular oedema (CMO) and subretinal fluid (SRF) with OCT findings, and to study the effect of photodynamic therapy (PDT) on the foveal morphology. METHODS: Patients with subfoveal, predominantly classic choroidal neovascularisation (CNV) secondary to age related macular degeneration (AMD) undergoing PDT were evaluated with refraction protocol best corrected logMAR visual acuity (VA), slit lamp biomicroscopy, stereoscopic fluorescein angiography (FFA), and OCT. New terminologies introduced to interpret the OCT scans were: neuroretinal foveal thickness (NFT), bilaminar foveal thickness (BFT), outer high reflectivity band thickness (OHRBT), intraretinal fluid (IRF), subretinal fluid (oSRF), and vitreomacular hyaloid attachment (VMHA). RESULTS: Fifty six eyes of 53 patients were studied. VA was better in eyes with a thinner outer high reflectivity band (OHRBT) (p = 0.02) and BFT (p = 0.05). BFT was less in eyes that had undergone a greater number of PDT treatments (p = 0.04). There was poor agreement between OCT and clinical examination in the detection of CMO and subretinal fluid (kappa = 0.289 and kappa = 0.165 respectively). To validate the interpretation and measurements on OCT, two groups of 20 scans were analysed by two independent observers. There was good agreement between the observers in the detection of IRF, oSRF, and VMHA (p<0.001). Measurements of NFT and BFT had a high reproducibility, and of OHRBT reproducibility was low. CONCLUSIONS: New terminology has been introduced and tested. OCT appears to be superior to clinical examination and FFA in the detection of CMO. In this study, better vision was associated with a thinner OHRBT and/or the absence of SRF giving insight into the biological effect of PDT.

Case selection in macular relocation surgery for age related macular degeneration.

BACKGROUND: To date there has been no randomised controlled trial demonstrating the safety and efficacy of macular relocation surgery (MRS) for age related macular degeneration (AMD). Vision can be improved in some patients and made worse in others despite successful surgery or because of complications. PURPOSE: To determine which patients would benefit from MRS. METHODS: Twenty nine patients with exudative AMD took part in a prospective, non-comparative, interventional study. Macular relocation surgery involved phacoemulsification, vitrectomy, 360 degrees retinotomy, excision of choroidal neovascular membrane, and macular relocation using an infusion of 5-fluorouracil and low molecular weight heparin as adjuvant to prevent proliferative vitreoretinopathy. Patients underwent protocol refraction preoperatively and six-monthly postoperatively by designated optometrists. Preoperative fundus fluorescein angiograms were read by masked observers and the lesions were classified according to a set protocol. The main outcome measures were visual improvement, final vision of better than 20/400, reading speed, critical print size. Logistic and multiple stepwise linear regressions were used to identify independent factors which predicted the main outcomes. RESULTS: Preoperative visual acuity (20/120 or worse) and lesion type (predominantly classic or submacular haemorrhage) were significantly associated with visual improvement (coefficient of regression B = 26.8, p<0.001 and B = 14.9 with p = 0.045 respectively). There were no significant independent factors which predicted a final distance logMAR visual acuity of 1.3 (20/400) or any arbitrary definition of blindness. CONCLUSIONS: The study showed that it was possible to select cases that were more likely to experience an improvement in vision following MRS.

Macular relocation after photodynamic therapy for recurrent choroidal neovascular membrane: visual results and histopathological findings.

BACKGROUND/AIMS: The findings in a patient treated with photodynamic therapy (PDT) followed by macular relocation surgery (MRS) are presented. METHODS: Histopathological evaluation of the choroidal neovascular membrane (CNV) specimen including immunohistochemical assessment. RESULTS: Microscopy revealed one CNV area that was richly vascular with attached retinal pigment epithelial cell monolayer and another area that was made up of densely collagenous avascular tissue with adherent fragments of Bruch's membrane and glial elements. CONCLUSION: The findings suggest that the PDT treated part of the CNV may have been adherent to the neuroretina and may have contributed to the formation of the macular hole. Caution is advised when considering MRS for CNV previously treated PDT.

Trypan blue staining of internal limiting membrane and epiretinal membrane during vitrectomy: visual results and histopathological findings.

AIMS: To report on the use of trypan blue (TB) 0.06% for staining the internal limiting membrane (ILM) and epiretinal membrane (ERM) during vitrectomy and report on their histology. METHOD: 14 consecutive patients with idiopathic macular hole or macular pucker (seven patients each) were prospectively recruited for ILM or ERM peel respectively. After pars plana vitrectomy and induction of posterior vitreous detachment, 0.5 ml TB 0.06% in phosphate buffered saline (VisonBlue) was injected over the posterior pole in an air filled eye and left for 2 minutes. The stained tissue was peeled with intraocular forceps. Specimens were evaluated using histochemical and immunohistochemical methods. RESULTS: The average follow up was 4.4 months. Internal limiting membranes and epiretinal membranes were stained satisfactorily in all cases and removed successfully. Eight patients (57%) had improvement of 2 or more Snellen lines. All seven macular holes closed. In the ERM cases, no residual membranes were observed clinically, at the latest follow up. No complications relating to the use of the dye were encountered intraoperatively or postoperatively. Of the 14 procedures, nine (four macular hole and five macular pucker) yielded sufficient tissue for histopathological evaluation. Histological and immunohistological assessment revealed that the morphology of these specimens was similar to that observed in macular hole ILM and macular pucker ERM removed without the aid of dye. CONCLUSION: TB staining facilitated the identification and delineation of ILM and ERM removal during the surgical management of macular holes and macular pucker. The visual outcome of this series and the specimens removed suggest they are no different from those without TB staining. Its use in posterior segment appears to be safe but further studies are required to investigate its long term safety.