Concentration of haemodynamic and inflammatory related cytokines in diabetic retinopathy.

AIM: There are changes in blood flow during the clinical stages of diabetic retinopathy with increasing leukostasis and secondary elaboration of cytokines. This study evaluated the vitreous concentrations of haemodynamic-related (endothelin-1 (ET-1) and nitric oxide (NO)), inflammatory and anti-inflammatory (interleukin-1 receptor antagonist, IL-1 Ra) cytokines in the diabetic patients (with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR)), compared them with those of control patients (full thickness macular hole, FTMH) and correlated to macular structural indices. METHOD: Vitreous samples from five FTMH patients representing normal controls were analysed together with the vitreous samples of 15 patients with NPDR and five with PDR. The vitreous concentrations of nitrite (total NO), ET-1, and prostacyclin was determined using ELISA kits (R&D Systems, Minneapolis, MN, USA) according to the manufacturer's instructions. A sandwich luminescent immunoassay technique was used to determine IL-1beta and IL-1 Ra concentrations. RESULTS: In the different clinical groups, there were no differences in the vitreous NO and prostacyclin concentrations. In NPDR, the median ET-1 concentration (0.7 pg/ml SD +/-0.8 pg/ml) was significantly reduced (P<0.05), compared to PDR (6.35 pg/ml SD +/-0.6 pg/ml) and FTMH (3.6 pg/ml SD +/-0.14 pg/ml). Its concentration also positively correlated with foveal thickness and macular volume (P<0.05) in patients with NPDR and macular oedema. IL-1 beta was detected in PDR, and diabetic patients demonstrated a lower concentration of the anti-inflammatory cytokine IL-1 Ra. CONCLUSION: Reduced concentrations of ET-1 in NPDR may reflect the haemodynamic changes of NPDR. The IL-1 Ra concentration suggests a change in the anti-inflammatory environment of the diabetic retina.

Diabetic cataract removal: postoperative progression of maculopathy--growth factor and clinical analysis.

BACKGROUND: Diabetic cataract extraction can be frequently complicated by macular oedema, progression of retinopathy, or development of iris neovascularisation. The pathogenesis of these complications may be the result of changes in the concentration of angiogenic and anti-angiogenic cytokines in the immediate postoperative period. The study aims to prospectively analyse this. METHODS: Uneventful phacoemulsification with intraocular lens implant was performed in seven eyes of six patients with diabetic retinopathy ranging from severe non-proliferative to quiescent proliferative. Patients were reviewed 1 day, 1 week, 1 month, and 3 months after surgery with fundus fluorescein angiography (FFA) and aqueous sampling. Each sample was analysed for VEGF, HGF, Il-1 beta (pg/ml), and PEDF (microg/ml) by sandwich ELISA. RESULTS: Clinically significant macular oedema (CSMO) occurred in one patient although increased macular hyperfluorescence occurred in three patients on FFA at 1 month. VEGF 165 concentration increased 1 day after surgery from a median baseline of 68 pg/ml (range 22-87 pg/ml) to 723 pg/ml (range 336-2071) at day 1. By 1 month it had decreased to 179 (range 66-811 pg/ml). HGF concentrations steadily increased over the month while IL-1 beta and PEDF concentrations demonstrated an acute rise on day 1 after surgery and then IL-1beta returned to baseline concentrations while PEDF decreased to below baseline. CONCLUSION: These results confirm altered concentrations of angiogenic and antiangiogenic growth factors after cataract surgery, which may induce subclinical and clinical worsening of diabetic maculopathy.

Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy vs macular argon photocoagulation.

INTRODUCTION: Focal macular photocoagulation for clinically significant macular oedema (CSME) is the proven method for treatment of this condition, but with little chance of visual improvement. Pars plana vitrectomy (PPV) may produce resolution of macular oedema and improvement in visual acuity. However, there have been no randomised trials to ascertain role of vitrectomy in the management of persistent CSME. METHODS: Patients with persistent CSME despite previous macular photocoagulation and Snellen visual acuity 6/15 to 6/60 were recruited. Dilated fundoscopy, best-corrected visual acuity including Early Treatment Diabetic Retinopathy Study (ETDRS) vision, ocular coherence tomography and fundus fluorescein angiography (FFA) at baseline and up to 12 months post-treatment was performed. Exclusion criteria were signs of posterior vitreous detachment, macular traction or the taut posterior hyaloid face syndrome, or macular ischaemia on FFA. In all, 20 patients were randomised (10 in each arm) to either standard macular photocoagulation or PPV and removal of the posterior hyaloid face. RESULTS: Of the 20 patients recruited, seven patients completed the protocol in the vitrectomy and eight in the laser arms, respectively. There was little evidence of any difference in the foveal thickness at 12 months between the two treatment arms despite a gradual improvement. Only one patient, from the vitrectomy arm, suffered moderate visual loss (defined as loss of 15 ETDRS letters) (our primary outcome). DISCUSSION: In this pilot RCT, standard PPV provides little visual benefit compared to macular photocoagulation, but a larger definitive study is required to confirm this early appraisal.

Pars plana vitrectomy for diabetic macular oedema: OCT and functional correlations.

PURPOSE: A prospective study to evaluate the macular structural and functional effects of pars plana vitrectomy (PPV) for persistent diffuse clinically significant macular oedema (CSMO). METHOD: A total of 12 patients with persistent diffuse CSMO were recruited and underwent assessment including best-corrected visual acuity, fundus fluorescein angiography, optical coherence tomography (OCT) and fine matrix mapping (FMM) at baseline and over a period of a year poststandard three-port PPV. RESULTS: The median baseline ETDRS letters score for all 12 patients was 52 (range 41-63) while at 12 months it had increased to 65 (range of 27-68), an improvement of two complete ETDRS lines (P=0.037). Similarly, there was an improvement in the perifoveal cone thresholds (P=0.02). The foveal thickening for all 12 patients ranged from a median of 183 to 751 microm (normal range 126-180 microm) and the macular volume ranged from a median of 2.13 to 6.42 mm(3) (normal <1.66 mm(3)). After surgery, both the median foveal thickness (from 334 to 280 microm) and median macular volume (from 3.24 to 2.61 mm(3)) demonstrated decreases over 12 months (P=0.01). On baseline OCT, the patients fell into two anatomically distinct groups: Group 1 (n=4) had a dome-shaped thickened macula with a partial posterior hyaloid separation and a significantly higher foveal thickness and macular volume than Group 2 (n=8) which had a diffuse low-elevation profile of the thickened macula (P=0.007). CONCLUSIONS: In this prospective study of PPV for persistent fovea-involving CSMO there was structural and functional improvement.

Angiopoietin concentrations in diabetic retinopathy.

BACKGROUND/AIM: Angiopoietin 1 and 2 interact with vascular endothelial growth factor (VEGF) to promote angiogenesis in animal and in vitro models. Although VEGF concentrations are elevated, there is little information regarding angiopoietin concentration in the vitreous of patients with diabetic retinopathy. METHODS: Angiopoietin concentrations were measured by luminescence immunoassay in vitreous samples from 17 patients with non-proliferative diabetic retinopathy (NPDR) and clinically significant diabetic macular oedema (CSMO), 10 patients with proliferative diabetic retinopathy (PDR), and five patients with macular hole (controls) obtained at pars plana vitrectomy. RESULTS: Angiopoietin 1 concentrations were low in patients with macular hole (median 17 pg/ml) while in NPDR with CSMO they were 2002 pg/ml (range 289-5820 pg/ml) and in PDR 186 pg/ml (range 26-2292 pg/ml). Angiopoietin 2 concentrations in NPDR with CSMO were a median of 4000 pg/ml (range 1341-14 329 pg/ml). For both macular hole and PDR patients angiopoietin 2 was below the limit of detection. CONCLUSIONS: Angiopoietin 2 concentration was twice that of angiopoietin 1 in NPDR with CSMO. Angiopoietin 2 is the natural antagonist of angiopoietin 1 which is thought to act as an anti-permeability agent. The predominance of angiopoietin 2 may allow VEGF induced retinal vascular permeability in patients with CSMO. The relatively low concentration of both angiopoietin 1 and 2 in patients with proliferative diabetic retinopathy may reflect the established nature of the neovascularisation in cases proceeding to vitrectomy.

Surgical blepharoptosis--the bridle suture factor?

AIMS: To evaluate the role of the superior rectus bridle suture in the development of post cataract blepharoptosis. METHODS: We compared the incidence of postoperative ptosis in two groups of patients undergoing cataract extraction. In the first group (32 patients), a temporal corneal approach was employed with no superior rectus bridle suture. In the second group (38 patients), a superior approach with a bridle suture was used. Both groups of patients underwent phacoemulsification with the use of peribulbar anaesthesia, a pressure lowering device and a speculum. We recorded the lid position at least 12 weeks following surgery and determined the degree of postoperative ptosis. Two-sided Fischer's Exact Test was used to test for significant difference between the two groups (using a statistical software package Instat Version 3.0 for Windows). RESULTS: Taking 2 mm of ptosis as a significant change, 11.5% of those undergoing temporal section sustained postoperative ptosis whilst it occurred in 12.9% of those who underwent a superior approach. CONCLUSIONS: The presence or absence of the superior rectus bridle suture and the site of the ocular wound do not significantly contribute to the incidence of postoperative ptosis. We would suggest that the causative factors are peribulbar anaesthesia, a pressure lowering device and the use of the speculum.

Dilated pupils and loss of accommodation following diode panretinal photocoagulation with sub-tenon local anaesthetic in four cases.

AIM: To describe pupillary abnormalities associated with diode laser photocoagulation with subTenon's local anaesthetic. METHODS: We describe four cases of tonic pupils following diabetic panretinal photocoagulation with subTenon's local anaesthetic. RESULTS: Six pupils of four patients became dilated and sustained loss of accommodation with denervation hypersensitivity with 0.1% pilocarpine after undergoing panretinal photocoagulation with a subTenon's local anaesthetic. The numbers of burns were not excessive and in one patient it even occurred after only 1200 laser burns. CONCLUSION: Diode laser causes histological changes deeper in the retina and the choroid than in Argon laser. Intense diode laser burns may cause damage to the short ciliary nerves traversing the choroid. In the unanaesthetised patient, pain arises when the laser burn hits these nerves and so may protect the eye from excess damage to the nerves. When the eye is anaesthetised with a subTenon's, local anaesthetic damage to the choroidal nerves may occur without the laser operator being aware that the burns are too intense.

Nitric oxide synthase in developing retinas and after optic tract section.

We compared the pattern of nitric oxide synthase (NOS) immunoreactivity in retinas of rats during normal development and after unilateral transection of the optic tract at postnatal day 7. NOS was first detected in the second postnatal week in the inner nuclear and inner plexiform layers. There was no detectable difference in the overall pattern of immunoreactivity between normal retinas and retinas with severe loss of ganglion cells due to the lesion. We suggest that NOS may have a role in synaptic and vascular development in the inner retina, but is unlikely to play a major role in normal physiological retinal ganglion cell death or axotomy-induced cell death.