A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth.

The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth. Notably, we found that increased neural activity led to a proteasome-dependent reduction in the levels of Ephexin5 in neuronal dendrites, which could facilitate the enhanced spine outgrowth observed following increased neural activity. Surprisingly, we also found that Ephexin5-GFP levels were elevated on the dendrite at sites of future new spines, prior to new spine outgrowth. Moreover, lowering neuronal Ephexin5 levels inhibited new spine outgrowth in response to both global increases in neural activity and local glutamatergic stimulation of the dendrite, suggesting that Ephexin5 is necessary for activity-dependent spine outgrowth. Our data support a model in which Ephexin5 serves a dual role in spinogenesis, acting both as a brake on overall spine outgrowth and as a necessary component in the site-specific formation of new spines.

Retina rejuvenation therapy for diabetic macular edema: a pilot study.

PURPOSE: To prospectively investigate the safety and efficacy of a novel frequency-doubled nanosecond-pulsed laser with discontinuous beam energy distribution (2RT, Ellex) for the treatment of diabetic macular edema. METHODS: Twenty-three consecutive patients (38 eyes) with newly diagnosed diabetic macular edema were recruited and assessed with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness measured with optical coherence tomography (OCT/scanning laser ophthalmoscope, OPKO/OTI), microperimetry, fundus photography, and fundus fluorescein angiography. Macular grid treatments were performed with 2RT laser system by 1 operator. Patients were examined with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness, microperimetry, and fundus photography at 3 weeks and 6 weeks and 3 months and 6 months. Fundus fluorescein angiography was repeated at 3 months and 6 months. RESULTS: Six months postoperatively, 17 patients (28 eyes) completed the study. No complications were identified after 2RT therapy. Intraoperative retinal discoloration was observed in 2 cases, fully resolved at 3 months with no permanent anatomical or functional changes. Mean logarithm of the minimum angle of resolution visual acuity improved from 20/44 at baseline to 20/27 at 6 months. The change in best-corrected visual acuity was significant (P = 0.0190). Central macular thickness in the central 1-mm subfield, retinal exudates and vascular leakage decreased in the majority of patients at 6 months (46, 41, and 55%, respectively), although the change from baseline was not statistically significant. Microperimetry confirmed photoreceptor integrity and showed a trend of improvement that correlated with decreased central macular thickness. CONCLUSION: For the first time, we achieved a beneficial effect on diabetic macular edema without the side effects of conventional laser therapy. The efficacy of this system in comparison with standard argon laser photocoagulation and in the treatment of other conditions affecting the retinal pigment epithelium needs further investigation.

Diabetic retinopathy--an historical review.

Diabetic macular changes in the form of yellowish spots and extravasations that permeated part or the whole thickness of the retina were observed for the first time by Eduard Jaeger in 1856. This was only possible as a result of the newly developed direct ophthalmoscope that was first described in 1855. Jaeger's findings were controversial at the time and Albrecht von Graefe openly claimed that there was no proof of a causal relationship between diabetes and retinal complications. It was only in 1872 that Edward Nettleship published his seminal paper "On oedema or cystic disease of the retina" providing the first histopathological proof of "cystoid degeneration of the macula" in patients with diabetes. In 1876, Wilhelm Manz described the proliferative changes occurring in diabetic retinopathy and the importance of tractional retinal detachments and vitreous haemorrhages. In the early years of the 20th century, the debate continued whether macular changes were directly related to diabetes or whether they were due to hypertension and arteriosclerosis. It was not until the second half of the century that the work of Arthur James Ballantyne in Glasgow provided more evidence that suggested that diabetic retinopathy represents a unique vasculopathy.

Phacoemulsification versus extracapsular cataract extraction in patients with diabetes.

OBJECTIVE: To compare phacoemulsification with extracapsular cataract surgery in patients with diabetes and to identify determinants of postoperative visual acuity. DESIGN: Prospective, randomized, paired-eye trial. PARTICIPANTS: Forty-six patients with diabetes and bilateral cataract. INTERVENTION: Patients were allocated to phacoemulsification surgery with silicone intraocular lens to one randomly determined eye, and extracapsular cataract surgery with 7-mm polymethylmethacrylate intraocular lens to the other. MAIN OUTCOME MEASURES: Logarithm of minimum angle of resolution visual acuity (logMAR VA), incidence of clinically significant macular edema (CSME), retinopathy progression, indices of anterior segment inflammation, and incidence of capsulotomy. RESULTS: Compared with eyes undergoing phacoemulsification, eyes managed with extracapsular surgery had more anterior chamber cells (P = 0.0004) and flare (P = 0.007) 1 week after surgery and a higher incidence of posterior synechiae (P = 0.04) and intraocular lens deposits (P < 0.0005) in the first postoperative year. The need for posterior capsulotomy was greater in eyes undergoing extracapsular surgery (16 of 46 vs. 5 of 46, P = 0.01). No difference in incidence of postoperative CSME, progression of retinopathy, or development of high-risk proliferative retinopathy was identified between techniques (P = 1.0, 0.8, and 0.2). Median 1-year logMAR VA was worse in eyes undergoing extracapsular surgery (0.08 vs. 0.06, P = 0.02), especially in those with retinopathy (0.14 vs. 0.08, respectively; P = 0.01). The presence or absence of CSME at the time of surgery was the most significant determinant of 1-year logMAR VA in regression models for both extracapsular (P = 0.0004, R2 = 0.45) and phacoemulsification groups (P < 0.00005, R2 = 0.46). CONCLUSIONS: Phacoemulsification is associated with better postoperative VA, less postoperative inflammation, and less need for capsulotomy than extracapsular cataract surgery in patients with diabetes. However, with both techniques, the principal determinant of postoperative VA appears to be the presence or absence of CSME at the time of surgery. Early intervention, reducing the risk that unrecognized CSME is present at the time of surgery, may be more critical to outcome than choice of surgical technique.

Clinical applications of the MicroPulse diode laser.

PURPOSE: To evaluate the efficacy of the Iris Oculight MicroPulse 810 nm diode laser in the treatment of macular oedema secondary to either branch retinal vein occlusion (BRVO) or diabetic maculopathy and in the treatment of proliferative diabetic retinopathy. The specific advantages of this type of laser delivery are greater retinal pigment epithelial specificity and less damage to the inner retina, thus preserving visual field and colour contrast sensitivity. METHODS: Fifty-two eyes of 33 consecutive patients were treated over a 6-month period. Thirteen eyes had proliferative diabetic retinopathy and 39 had macular oedema secondary to BRVO or diabetic maculopathy. Panretinal and grid pattern photocoagulation were performed using the micropulse mode with the laser on for 100-300 microseconds and off for between 1900 and 1700 microseconds repeatedly in a pulse envelope of 0.1-0.3 s duration. Microaneurysms were not treated directly. Patients were assessed clinically and angiographically at 3 and 6 months. RESULTS: Ten eyes (77%) with proliferative disease showed some regression of new vessels at 6 months. Twenty-two eyes (57%) showed resolution of macular oedema at 6 months. Visual acuity was maintained in 27 eyes (69%) and improved in 11 eyes (28%). CONCLUSION: Diode laser in micropulse mode is effective in the management of diabetic and occlusive macular oedema and proliferative diabetic disease.

Panretinal photocoagulation during cataract extraction in eyes with active proliferative diabetic eye disease.

PURPOSE: Cataract surgery in the presence of active proliferative diabetic eye disease carries a high risk of progression of retinopathy and neovascular glaucoma. Lens opacities may prevent panretinal photocoagulation (PRP) before surgery, and applying PRP in the immediate post-operative period can be difficult. The purpose of this study is to report results of cataract extraction combined with per-operative indirect laser PRP in a group of these patients. METHODS: Nine eyes of 9 diabetic patients with active retinal or iris neovascularisation in which lens opacities prevented adequate pre-operative PRP underwent cataract surgery combined with indirect laser PRP after cortex aspiration and before intraocular lens implantation. RESULTS: Regression of neovascularisation with this combined procedure alone was achieved in 5 eyes, 3 responded to further PRP, and 1 developed neovascular glaucoma. Visual acuity improved in all eyes, 4 achieving > or = 6/12. Four patients developed increased post-operative uveitis. One developed clinically significant macular oedema. CONCLUSIONS: The method described has definite practical advantages over PRP attempted in the immediate post-operative period, when many factors can prevent its application or reduce its effectiveness, and when neovascularisation may be progressing rapidly. In addition, adjunctive per-operative indirect laser PRP appears to improve the outcome of cataract surgery in eyes with active proliferative diabetic eye disease.

The natural history of macular edema after cataract surgery in diabetes.

OBJECTIVE: To determine the natural history of macular edema after cataract surgery in diabetes to provide a rational basis for laser therapy. DESIGN: Prospective clinical and angiographic trial. PARTICIPANTS: Thirty-two patients with diabetes undergoing cataract surgery. INTERVENTION: Phacoemulsification surgery with intraoperative fluorescein angiography, and postoperative clinical and angiographic assessment without macular laser therapy for 1 year after surgery. MAIN OUTCOME MEASURES: Clinically significant macular edema, postoperative macular and optic disc hyperfluorescence relative to the intraoperative angiogram, and logarithm of the minimum angle of resolution (LogMAR) visual acuity. RESULTS: In the first postoperative year, macular fluorescence remained at its intraoperative level in 2 (6%) of 32 eyes and increased in 30 (94%) of 32 eyes, returning to its intraoperative level within 1 year of surgery in 13 (43%) of 30 eyes. Optic disc fluorescence remained at its intraoperative level in 2 (6%) of 32 eyes, was not graded in 3 (9%) of 32 eyes, and increased in 27 (84%) of 32 eyes, returning to its intraoperative level within 1 year of surgery in 19 (70%) of 27 eyes. Clinically significant macular edema was identified in the first postoperative year in 18 (56%) of 32 eyes, being present at the time of surgery in 5 eyes and arising de novo within 1 year of surgery in 13 eyes. It resolved spontaneously within 1 year of surgery in 0 of 5 eyes in which it had been present at the time of surgery and in 9 (69%) of 13 eyes in which it arose in the first 6 months after surgery (P = 0.05). Angiographic and clinical resolutions of macular edema were less likely in eyes with more severe retinopathy at the time of surgery (P = 0.03, 0.005). One-year LogMAR acuity of 0.3 or less (> or = 20/40) was achieved in 27 (84%) of 32 eyes. Clinically significant macular edema at the time of surgery was associated with poorer 1-year visual acuity in multivariate analysis (P = 0.005, r2 = 0.5). CONCLUSIONS: Clinically significant macular edema present in diabetic eyes at the time of cataract surgery is unlikely to resolve spontaneously, but clinically significant macular edema arising after surgery commonly resolves, particularly if retinopathy is mild. These findings have implications for the timing of cataract surgery in diabetes and postoperative macular laser therapy. Ophthalmology 1999;106:663-668

Ocular manifestations of diabetes mellitus.

The ocular complications of diabetes mellitus are numerous and include retinopathy, cataract, uveitis, and neurophthalmic disorders. A review of the current literature shows that the emphasis has changed from the laser and surgical management of pre-existent retinopathy to the development of cohesive multidisciplinary screening and education programs, and to a better understanding of the cellular and molecular mechanisms that underlie disease. The role of associated and potentially modifiable systemic factors is also now recognized. Early intervention with systemic and local therapies may soon provide hope for the better management of diabetic eye disease.

Micropulse laser in the treatment of diabetic macular edema.

The micropulse laser is a new development in laser therapy. Micropulsing is frequent short pulses of subthreshold intensity applied to retinal lesions. It has been shown to be effective in diabetic macular edema, branch vein occlusion, and drusen. Although the initial landmark studies showed it to be effective, the exact parameters have not been established. This article illustrates the current state of its use.

Hipotensäo intracraniana espontânea: relato de caso / Spontaneous intracranial hypotension: case report

Descrevemos o caso de um paciente de 45 anos de idade com cefaléia postural secundária a hipotensao liquórica espontânea, no qual a ressonância nuclear magnética do crânio revelou impregnaçao de contraste e espessamento meníngeo.

Long-term results after drainage of premacular subhyaloid hemorrhage into the vitreous with a pulsed Nd:YAG laser.

OBJECTIVE: To investigate the effects of drainage of premacular subhyaloid hemorrhage into the vitreous with an Nd:YAG laser in a large series of patients with long-term follow-up. METHODS: A retrospective review was conducted on 21 eyes with a circumscribed premacular subhyaloid hemorrhage of various causes. These eyes were treated with a pulsed Nd:YAG laser to drain the entrapped blood into the vitreous. The period of review ranged from 12 to 32 months (mean, 22 months). RESULTS: In 16 eyes, visual acuity improved within 1 month. Four eyes had persistent, dense, nonclearing vitreous opacity for at least 3 months and finally required vitrectomy. One clotted hemorrhage did not drain into the vitreous. Final visual outcome was determined by the underlying diagnosis, such as Valsalva retinopathy (7 eyes), diabetic retinopathy (7 eyes), branch retinal vein occlusion (4 eyes), and retinal macroaneurysm, Terson syndrome, or blood dyscrasia (1 eye each). Eyes with Valsalva retinopathy fared the best. Complications included a macular hole in 1 eye and a retinal detachment from a retinal break in a myopic patient. CONCLUSIONS: Drainage of premacular subhyaloid hemorrhage into the vitreous with an Nd:YAG laser is a viable treatment alternative for eyes with recent bleeding. However, a macular hole and a retinal detachment were observed as complications. Thus, to establish Nd:YAG laser treatment as a routine procedure, the risks and benefits have to be weighed in a randomized trial and compared with those of deferral of treatment or primary vitrectomy.

Partial laser ablation of massive peripapillary subretinal neovascularization.

BACKGROUND: Although peripapillary subretinal neovascular membranes (PSRNs) are less common and often larger than neovascular complexes arising near the fovea, they may lead to severe visual loss. Very large (massive) PSRNs (MPSRNs) are 3.5 disc areas or greater in overall size, are even less common, and may contain a significant occult component, leading to slow and unpredictable growth. Such massive lesions may begin at the nasal margin of the disc and do not become symptomatic until they have extended around the disc toward the macula, threatening central vision. Although complete laser ablation has been used for symptomatic PSRNs with variable success, the optimal treatment of MPSRNs remains controversial. METHODS: The authors reviewed the clinical course of 12 eyes of seven patients with MPSRNs. Ten eyes received laser treatment, which was limited to the temporal portion of the subretinal neovascular complexes only and two received no treatment. RESULTS: Of the ten eyes receiving laser treatment, six showed stabilization of visual acuity, whereas in four the neovascular membrane progressed beneath the fovea with severe visual loss. In the two untreated eyes, the subretinal neovascular membrane progressed beneath the macula with the loss of central vision. CONCLUSIONS: In contrast to the small symptomatic PSRNs, which are usually treated by complete laser ablation, MPSRNs may stabilize with only partial laser treatment. However, both types of lesions may remain stable for long periods of time without any treatment and require treatment only if progression toward the fovea occurs.

The venous closing pressure in central retinal vein obstruction.

OBJECTIVE: To assess the rate of change in the central retinal venous closing pressure in central retinal vein obstruction over time, and its relationship to visual acuity improvement and the development of rubeosis iridis. METHODS: Fifty patients presenting with central retinal vein obstruction of less than three months' duration, between the ages of 40 and 80 years, were reviewed prospectively. The central retinal venous closing pressure was measured by digital ocular compression. Patients were discharged from the study after the six-month visit. RESULTS: All patients had elevated venous closing pressure at presentation, whereas at six months only 24 patients had persistent elevation. Of 16 patients with lowering of the venous closing pressure within four months of onset of central retinal vein obstruction, 11 (69%) had two or more lines of visual acuity improvement. Only two of 10 patients (20%) developing lowering of the venous closing pressure thereafter had visual improvement. No patient developed rubeosis iridis after the venous closing pressure lowered. CONCLUSION: The central retinal venous closing pressure is raised in central retinal vein obstruction to about central retinal arterial diastolic pressure, and is its pathognomonic sign. This sign is easily elicited via digital pressure on the eyelid, and has prognostic significance for visual acuity improvement and the development of rubeosis iridis.

Extracapsular cataract surgery with and without intraocular lens implantation in Fuchs heterochromic cyclitis.

PURPOSE: To compare the surgical and postoperative complications and visual outcome of extracapsular cataract extraction (ECCE) with and without intraocular lens (IOL) implant in Fuchs heterochromic cyclitis. METHODS: The records of 77 patients with Fuchs heterochromic cyclitis who had undergone ECCE were reviewed. Of a total of 77 eyes, a posterior chamber IOL (PC IOL) was implanted in 43 eyes, whereas 34 eyes did not receive an implant. RESULTS: In the pseudophakic group, 40 (93%) eyes achieved 20/40 or better. This level also was achieved in 29 (85%) eyes not receiving an implant. Intraoperative anterior chamber hemorrhage was documented in 18 eyes but there was no correlation with preoperative gonioscopic findings. A temporary or permanent elevation of intraocular pressure was noted in five of eight eyes that had marked anterior chamber hemorrhage. Severe postoperative uveitis occurred in ten eyes and was more common in patients with glaucoma who had PC IOL implantation, but this did not adversely affect the visual outcome. Of 40 eyes with PC IOL implant, severe postoperative uveitis developed in 7. In six of these seven eyes, the implant was a three-piece lens with polypropylene haptics. Severe postoperative uveitis developed in 6 of 16 eyes with preoperative glaucoma. Five of these six eyes had a PC IOL implant. Of the 34 aphakic patients, 10 (29%) were intolerant of contact lens correction. There was no difference in the incidence of postoperative uveitis, cystoid macular edema, and development of glaucoma between the two groups. CONCLUSION: Implantation of PC IOLs in ECCE in patients with Fuchs heterochromic cyclitis appears to a safe procedure, but careful postoperative follow-up of intraocular pressure, particularly in patients with intraoperative hemorrhage or postoperative uveitis, is indicated.

Is the first day postoperative review necessary after cataract extraction?

BACKGROUND: In current ophthalmic practice day-case surgery cataract patients are conventionally discharged and then reviewed the following morning thus limiting the advantages of what 'true' day-case surgery strives to achieve. The aim of this study was to see if there was a difference in outcome between 'true' day-case cataract surgery and non-day-care surgery. METHODS: A total of 387 consecutive cataract operations were followed, comprising 122 local anaesthetic day-cases, 149 local anaesthetic non-day-cases, 63 general anaesthetic non-day-cases, and 53 general anaesthetic day-cases. RESULTS: Although not randomised the groups were comparable with respect to age, operator grade, sex, presence of diabetes, anaesthetic type, pre and postoperative visual acuities, and time to first planned outpatient visit. There were 10 early postoperative complications in the day-case group (5.71% of total) and 14 in the non-day-case group (6.6% of total), the commonest complications in both groups were raised intraocular pressure, corneal oedema, and wound leaks. One patient in each group had an early complication that necessitated attending the casualty department. The visual outcomes in both groups were comparable. CONCLUSIONS: These findings suggest that there were no preventable complications within the constraints of the number of operations studied and that no additional risk is attached to 'true' day-case surgery relative to non-day-case surgery.