Cellular migration, proliferation, and contraction. An in vitro approach to a clinical problem--proliferative vitreoretinopathy.

Presently used animal models of proliferative vitreoretinopathy reflect only cell proliferation and contraction. We used an in vitro model that measured cell migration, proliferation, and contraction. The following four drugs were assayed on this system: daunomycin, taxol, colchicine, and cytochalasin B. Daunomycin was the most effective drug against cell proliferation and cell migration but had no effect on cell contraction; taxol and colchicine affected all three parameters. Cytochalasin B was the least effective drug tested.

Use of indomethacin for pain relief following scleral buckling surgery.

BACKGROUND/AIMS: Patients undergoing scleral buckling and cryotherapy suffer from mild to moderate postoperative pain. As good pain relief facilitates post-operative ocular examination, as well as patient comfort and recovery, the authors designed a prospective randomised double masked trial to evaluate the efficacy of indomethacin as a satisfactory analgesic for such patients. METHOD: Patients with a primary uncomplicated rhegmatogenous retinal detachment requiring scleral buckling and cryotherapy were randomly allocated to receive either indomethacin or placebo. A rectal suppository was administered 2 hours before surgery, followed by two capsules twice daily for 10 days. Pain relief was assessed with a linear graphic rating scale at the end of each day. Supplementary analgesia was allowed and recorded. RESULTS: 12 patients received indomethacin (group A) and 16 received placebo (group B). The extent of surgery was similar in both groups. One patient in group A, and two in group B withdrew after 3 days. The pain scores were converted to changes from the baseline (score on day 1), and the area under the curve calculated for each patient. The means of the areas were analysed with the Mann-Whitney test and showed that indomethacin caused a statistically significant reduction in pain score, both at 3 days (p = 0.04) and at 10 days (p = 0.014). There was no statistically significant difference in extra analgesic requirements between the two groups (p = 0.2). CONCLUSIONS: Indomethacin is recommended for short to medium term pain relief following scleral buckling and cryotherapy.

Anatomical and visual outcome of retinal detachment surgery in children.

AIMS: To evaluate the visual and anatomical outcome, as well as complications following surgery, for rhegmatogenous retinal detachment in children at a tertiary referral centre over a 5 year period. METHODS: A retrospective survey of all children (aged 0-16 years) who underwent primary retinal detachment surgery at Queen's Medical Centre between April 1994 and March 1999. RESULTS: 15 consecutive patients were identified with a mean follow up of 14.7 months (range 3-57) and a mean age of 12.4 years. Trauma was the cause in 40% (6/15). Complete retinal reattachment was achieved in 86.6% (13/15). Visual improvement occurred in 53.3% (8/15), worsening of vision occurred in 13.3% (2/15), with no change in the remaining 33.3% (5/15). Visual acuity was D 6/12 in 6.6% (1/15) preoperatively, and 26.6% (4/15) postoperatively. CONCLUSIONS: Retinal detachment in children is rare compared with adults. There are therefore limited data available for this group of patients. These data provide one unit's experience over a 5 year period, and may help provide a basis for information for patients and their parents when discussing the risks and potential benefits of surgery for retinal detachment in the paediatric population.

Intravitreal invading cells contribute to vitreal cytokine milieu in proliferative vitreoretinopathy.

AIM: To examine the contribution of infiltrating cells in the local production of cytokines within the vitreous of patients with proliferative vitreoretinopathy (PVR). METHODS: The presence of mRNA coding for IL-6, IL-8, IL-1beta, IL-1alpha, TNFalpha, IFNgamma, IL-12, and HPRT was investigated in 25 vitreous samples from patients with PVR, 11 vitreous samples from patients with retinal detachment (RD) not complicated by PVR, and 10 vitreous samples from patients with macular hole (MH). A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using an internal competitor was used to investigate these samples. From these samples, 15 PVR, 8 RD, and 8 MH were analysed for the protein levels of the same cytokines using enzyme linked immunosorbent assay (ELISA). Spearman correlation was used to test any association between mRNA and cytokine protein levels, as an indicator of the contribution these cells make to the intravitreal cytokine milieu. RESULTS: A strong correlation was found between mRNA and their respective cytokine levels (protein products) for IL-6, IL-8, IL-1beta, IL-1alpha, TNFalpha, IFNgamma (Spearman r = 0.83, 0.73, 0.67, 0.91, 0.73, and 0.73 respectively), but not for IL-12. The median levels of IL-6, IL-8, IL-1beta, and IFNgamma mRNA and their respective cytokines were significantly higher (p <0.05) in patients with PVR than in those with macular hole. There was no statistically significant difference in the median levels of IL-1alpha mRNA between PVR and MH but the cytokine IL-1alpha was detected at a significantly higher level in PVR compared with MH patients. Between PVR and RD patients, there was no statistically significant difference in mRNA levels for all the investigated cytokines (p >0.05) except for IL-6 where there was a statistical significance (p= 0.038). In contrast, the median levels of IL-6, IL-8, and IL-1beta cytokines were significantly higher (p <0.05) in patients with PVR than in those with RD, whereas for IL-1alpha and IFNgamma no significant statistical difference was detected between PVR and RD patients (p >0.05). When results of RD and MH patients were compared, a statistical difference was only detected in mRNA levels of INFgamma (p = 0.008). However, no difference was detected for INFgamma (protein product) or for any of the other cytokines between RD and MH patients. CONCLUSION: Levels of both protein and mRNA encoding IL-6, IL-8, IL-1beta, and IFNgamma is significantly increased in vitreous samples from patients with PVR. The strong correlation between ELISA detectable cytokines (protein products) and their respective mRNA levels suggest that intravitreal, invasive cells are the major source of these cytokines, with the exception of IL-12. Cells invading the vitreous do not appear to locally produce IL-12 mRNA. This would appear to implicate cells peripheral to the vitreal mass as the major source of this cytokine.

Detection of cytokine mRNA production in infiltrating cells in proliferative vitreoretinopathy using reverse transcription polymerase chain reaction.

AIMS: To determine whether the infiltrating cells in the vitreous and subretinal fluid of patients with proliferative vitreoretinopathy (PVR) express messenger RNA for various cytokines found in this condition. METHODS: The presence of mRNA coding for HPRT, IL-6, IL-1beta, IL-8, and TNFalpha was investigated in 20 vitreous and subretinal fluid (SRF) samples from patients with PVR by reverse transcriptase polymerase chain reaction (RT-PCR). 16 samples from patients with retinal detachment and macular holes were used as controls. RESULTS: HPRT was detected in all samples of PVR and in 11 (69%) control cases. Patients with PVR demonstrated mRNA for the cytokines tested more often than controls. The difference was statistically significant. CONCLUSION: The presence of mRNA encoding for IL-6, IL-1beta, IL-8, and TNFalpha is significantly detected by RT-PCR in vitreous and SRF samples of patients with PVR, indicating local production of these cytokines by vitreous and SRF cells.

Association of macular involvement with proliferative retinopathy in Type 2 diabetes.

AIMS: To determine whether documented evidence of pre-existing maculopathy is present in Type 2 diabetic patients who require photocoagulation or vitrectomy for proliferative disease. This is a retrospective case notes review. METHODS: The study was performed at Queen's Medical Centre, UK. All patients listed in the laser register and operating theatre register over 5 years (March 1994 to March 1999) who had undergone pan retinal photocoagulation (PRP) for diabetic retinopathy, in one consultant firm, were studied. The medical records of patients who had undergone vitrectomy as their first treatment for proliferative diabetic retinopathy in a vitreo-retinal firm over the 5 years were examined. The proportion of patients with documented maculopathy before development of proliferative retinopathy was determined. RESULTS: All except 1/134 or 0.7% (95% confidence interval 0.1-4.5%) patients had documentation of macular signs in at least one eye prior to the patient's first session of PRP. Of the remaining 133, 104 (78%) had had focal or grid photocoagulation of the macula. The median time between the documentation of maculopathy before the first PRP treatment session was 16 months (interquartile range 7-36). Fourteen patients had vitrectomy and endolaser performed as the initial treatment for proliferative disease. All patients had documented maculopathy before the onset of proliferative disease. CONCLUSIONS: The results of this study suggest that in Type 2 diabetes, proliferative disease occurs relatively late compared with maculopathy. In such patients, maculopathy is almost invariably present when proliferative disease is detected.

Vitreous surgery in the management of chronic endogenous posterior uveitis.

OBJECTIVES: There is evidence that pars plana vitrectomy (PPV) has a beneficial effect on the clinical course of chronic endogenous posterior uveitis (EPU) possibly by physically removing any resident inflammatory cells with the vitreous. We assessed the anatomical and therapeutic effects of PPV performed on patients with chronic EPU for any indication. PATIENTS AND METHODS: Retrospective review of 41 eyes of 38 consecutive patients with EPU who underwent a PPV for any reason, over a 5-year period. The mean age of the patients was 36.2 years, 46% of the eyes had intermediate uveitis, 32% panuveitis, and 22% posterior uveitis. The visual acuity, disease activity, and the requirement for medications to control it were recorded for 12 months pre- and postoperatively. RESULTS: Overall, 61% of the eyes gained more than 2 Snellen lines (P<0.001) and the incidence of cystoid macular oedema (CMO) significantly reduced from 44 to 20% (P<0.05). Postoperatively, there was a significant decrease in the recurrence rate of intermediate uveitis, posterior uveitis, and panuveitis (P<0.001). The use of systemic and local depot immunosuppressive agents did not change over the study period, although the use of topical agents increased (P<0.05). CONCLUSION: PPV appears to have a beneficial effect on the clinical course of EPU in selected cases. This may be mediated by the physical clearance of inflammatory debris, the anti-inflammatory effect of replacing vitreous by aqueous humour, by a reduction of CMO and/or the anatomical correction of sight-threatening retinal pathology.

The effects of vigabatrin on electrophysiology and visual fields in epileptics: a controlled study with a discussion of possible mechanisms.

PURPOSE: To compare the visual electrophysiology and visual fields of patients taking vigabatrin to those of a control group of epileptics on other anti-epileptic drugs (AEDs). METHODS: Fourteen epileptics treated with vigabatrin and 10 control patients treated with other AEDs underwent ERG and EOG. Goldmann visual fields were performed and analysed using standard software to measure areas contained within I4e isopters. RESULTS: The cone and rod b-waves of the ERG, the oscillatory potential amplitudes and Arden indices were reduced in vigabatrin-treated subjects and the oscillatory potentials delayed. The Arden indices were reduced due to an increased dark trough. The areas contained within the I4e isopter of vigabatrin treated subjects were reduced compared to the control group and these areas correlated well with oscillatory potential amplitudes and b-wave amplitudes in the vigabatrin group only. CONCLUSIONS: The use of vigabatrin is associated with a reduction of the ERG cone b-wave amplitude and oscillatory potentials which correlates with visual field loss. The Arden ratio is reduced in subjects taking vigabatrin but may recover after cessation. However, visual loss may persist in the presence of a recovered EOG. These findings suggest further effects of the drug than those mediated by GABA receptors, and support the contention that the cause of the field loss may be at least in part due to retinal effects. Possible mechanisms are discussed.

Incidence of idiopathic full-thickness macular holes in fellow eyes. A 5-year prospective natural history study.

PURPOSE: This study aimed to determine the incidence of idiopathic full-thickness macular hole (FTMH) in normal fellow eyes and to evaluate the role of electrodiagnostic and psychophysical tests in identifying eyes at risk. PATIENTS AND METHODS: A prospective longitudinal natural history study of a cohort of patients with unilateral holes and normal, asymptomatic fellow eyes without posterior vitreous detachment was conducted. Subjects underwent baseline examination, pattern reversal electroretinography, electro-oculography (EOG), and color contrast sensitivity (CCS) testing for protan, deutan, and tritan thresholds and were recalled for clinical examination at 18 months and 5 years. RESULTS: At baseline, 114 patients were examined. Eighty were available for review at 18 months, of whom 6 had full-thickness macular holes develop in the fellow eye. At 5 years, 67 of the remaining 74 patients who had not developed holes at 18 months were re-examined and a further 5 were found to have holes develop in the fellow eye. A posterior vitreous detachment without hole formation had developed in 20 fellow eyes at 5 years. Although mean pattern reversal electroretinography and EOG responses were within normal limits in affected and fellow eyes at baseline, mean CCS protan, deutan, and tritan thresholds were elevated significantly in affected eyes at baseline (P = 0.0001). Unaffected fellow eyes showed normal mean protan and deutan thresholds, but significantly elevated mean tritan thresholds (P = 0.01) at baseline. Mean tritan CCS loss was, however, similar in fellow eyes in which holes later developed and in fellow eyes in which holes did not. CONCLUSIONS: The Kaplan-Meier estimated risk of fellow eye involvement is 15.6% (range, 8.4%-22.3%; P = 0.05) at 5 years. Although electrodiagnostic and psychophysical testing was not predictive of fellow eye involvement, tritan CCS loss at baseline, in apparently normal fellow eyes, may indicate subclinical foveal dysfunction, the nature of which is unclear.