Neurotrophic keratopathy and diabetes mellitus.

Diabetes mellitus is frequently associated with microvascular complications such as retinopathy, nephropathy, and peripheral neuropathy. Neurotrophic keratopathy occurs in response to a neuropathy of the ophthalmic division of the trigeminal nerve. Rarely has diabetic neurotrophic keratopathy been described. This paper discusses the ophthalmic histories of three patients who presented with diabetic neurotrophic keratopathy. In one patient the corneal ulceration was the sole presenting feature of his diabetes. We discuss the need for increased vigilance in the ophthalmic community for suspecting diabetes in patients with unexplained corneal epithelial disease.

Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy: effects of laser photocoagulation and angiotensin receptor blockade.

BACKGROUND: Proliferative diabetic retinopathy (PDR) may be a response to abnormal angiogenic growth factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and the soluble angiopoietin receptor tie-2. The authors hypothesised the following: (a) there are differences in plasma levels of these growth factors in different grades of diabetic retinopathy; and (b) that the effects of intervention with panretinal laser photocoagulation (PRP) for PDR, and angiotensin receptor blockade (using eprosartan) for patients with other grades of diabetic retinopathy will be to reduce levels of the growth factors. METHODS: Cross sectional and interventional study (using PRP and eprosartan) in diabetic patients. VEGF, Ang-2, and tie-2 were measured by ELISA. RESULTS: VEGF (p<0.001) and Ang-2 levels (p<0.001) were significantly higher in 93 diabetic patients compared to 20 healthy controls, with the highest levels in grade 2 and grade 3 diabetic retinopathy (p<0.05). Tie-2 was lower in diabetics compared to controls (p = 0.008), with no significant differences between the diabetic subgroups. Overall, VEGF significantly correlated with Ang-2 (p<0.001) and tie-2 (p = 0.004) but the correlation between Ang-2 and tie-2 levels was not significant (p = 0.065). Among diabetic patients only, VEGF levels were significantly correlated with Ang-2 (p<0.001) and tie-2 (p<0.001); the correlation between Ang-2 and tie-2 levels was also significant (p<0.001). There were no statistically significant effects of laser photocoagulation on plasma VEGF, Ang-2, and tie-2 in the 19 patients with PDR, or any effects of eprosartan in the 28 patients with non-proliferative diabetic retinopathy. CONCLUSION: Increased plasma levels of VEGF and Ang-2, as well as lower soluble tie-2, were found in diabetic patients. The highest VEGF and Ang-2 levels were seen among patients with pre-proliferative and proliferative retinopathy, but there was no relation of tie-2 to the severity of retinopathy. As the majority of previous research into Ang-2 and tie-2 has been in relation to angiogenesis and malignancy, the present study would suggest that Ang-2 and tie-2 may be used as potential indices of angiogenesis in diabetes mellitus (in addition to VEGF) and may help elucidate the role of the angiopoietin/tie-2 system in this condition.

Hypertension and the eye: changing perspectives.

Systemic hypertension is a common condition associated with significant morbidity and mortality. Hypertension confers cardiovascular risk by causing target-organ damage that includes retinopathy in addition to heart disease, stroke, renal insufficiency and peripheral vascular disease. The recognition of hypertensive retinopathy is important in cardiovascular risk stratification of hypertensive individuals. This review reevaluates the changing perspectives in the pathophysiology, classification and prognostic significance of fundal lesions in hypertensives.

Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction.

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis, hemorheologic factors, endothelial damage/dysfunction, and age-related macular degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), and von Willebrand factor (a marker of endothelial dysfunction) were measured. RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects than the controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the subjects (both P < 0.0001). There were no significant differences in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28) and "exudative" (n = 50) ARMD subjects were compared, there was no significant differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels. There were no significant correlations between the measured parameters. Stepwise multiple regression analysis did not demonstrate any significant clinical predictors (age, gender, smoking, body mass index, history of vascular disease, or hypertension) for plasma VEGF or fibrinogen levels, although smoking status was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS: This study suggests an association between markers of angiogenesis (VEGF), hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Idiopathic polypoidal choroidal vasculopathy: a disease with diverse clinical spectrum and systemic associations.

PURPOSE: To report the clinical findings, angiographic results, clinical course, response to laser photocoagulation and systemic-associations in a group of patients with idiopathic polypoidal choroidal vasculopathy (IPCV). METHODS: All patients with IPCV attending the macular clinic underwent a complete ocular examination, and fluorescein and indocyanine green angiography. In addition, a systemic examination including blood pressure, full blood count, plasma viscosity and coagulation status of patients was carried out. RESULTS: We present a series of 5 patients (7 eyes) with clinical and angiographic evidence of IPCV with follow-up of 3-6 years. We report diverse demographic and clinical manifestations. One patient had polypoidal lesions found at the peripheral retina (anterior to equator) of both eyes. Three patients were treated with laser photocoagulation and achieved stable vision; 2 patients who had no laser treatment experienced deteriorated vision, one of whom had a vitrectomy. One patient was hypertensive, 2 patients were found to have raised plasma viscosity, and 1 patient had thrombocytopenia. CONCLUSIONS: The clinical spectrum of IPCV is wider than previously documented. It is a distinct clinical entity which should be differentiated from other forms of haemorrhagic and exudative maculopathy. The availability of indocyanine green angiography has allowed increased recognition of these cases. Early selective laser treatment on lesions affecting maculae-could stabilise the disease. Its association with systemic cardiovascular disease and blood disorder may predispose to the recurrence of haemorrhagic events in this entity.

Plasma VEGF and soluble VEGF receptor FLT-1 in proliferative retinopathy: relationship to endothelial dysfunction and laser treatment.

PURPOSE: To study plasma levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), its soluble receptor (sFlt-1) and von Willebrand factor (vWf, an index of endothelial damage or dysfunction) in patients with proliferative retinopathy and corresponding changes in plasma levels after pan-retinal photocoagulation (PRP). METHODS: Eighteen patients (10 men; age, 57+/-16 years, mean +/- SD) with proliferative retinopathy secondary to diabetes (n = 13) and ischemic retinal vein occlusion (n = 5) with no previous PRP therapy were studied. Blood samples were obtained before and at 4 months after the last PRP session. Baseline (prelaser) plasma levels of VEGF, sFlt-1, and vWf (all by ELISA) were compared with levels in 16 diabetic patients with background retinopathy ("hospital controls"), and 18 healthy, age- and sex-matched "healthy controls." RESULTS: Patients with proliferative retinopathy had significantly raised plasma VEGF when compared with both control groups (P = 0.001). Patients with proliferative retinopathy and hospital controls had significantly raised plasma vWf levels when compared with healthy controls (P = 0.012). There was no difference in sFlt-1 levels between patients and controls (P = 0.162). After PRP, there was a significant reduction in plasma VEGF levels at 4 months' follow-up (P < 0.001), but no significant changes in plasma sFlt-1 or vWf levels. Patients with complete resolution of neovascularization had a trend toward lower median VEGF levels (80 versus 150 pg/ml, P = 0.062), but vWf levels (P = 0.50) and sFlt-1 (P = 0.479) were not statistically different. Baseline VEGF and sFlt-1 levels were significantly correlated (Spearman r = 0.505, P = 0.032) but after PRP at 4 months' follow-up, this was no longer significant (r = -0.269, P = 0.28). CONCLUSIONS: In this pilot study, patients with proliferative retinopathy demonstrate elevated peripheral markers of angiogenesis and endothelial dysfunction, suggesting a role for these processes in the pathogenesis of this condition. A fall in levels of VEGF after successful laser treatment may provide an opportunity for monitoring disease progression or relapse via a blood sample.

Polyarthropathy, orbital myositis and posterior scleritis: an unusual adverse reaction to influenza vaccine.

We report a patient who developed an acute symmetrical polyarthropathy, orbital myositis and posterior scleritis following inoculation with the 1993 Fluvirin (inactivated influenza vaccine: surface antigen) vaccine. We believe that this represents a hypersensitivity reaction to the vaccine as extensive investigations revealed no underlying infective, inflammatory or systemic cause. We review the current indications for vaccination against the influenza virus and the known adverse reactions to the vaccine.

Long-term follow-up of a single continuous adjustable suture in penetrating keratoplasty.

Penetrating keratoplasty was performed on 30 patients using a single adjustable continuous 10/0 nylon suture. Seventeen patients had astigmatism of 4.00 dioptre cylinders (DC) or more and were adjusted. The latest adjustment was at 32 weeks. Following adjustment there was a significant reduction in median post-keratoplasty astigmatism from 6.00 DC to 2.50 DC (p < 0.001). Thirteen patients, with astigmatism of 4.00 DC or less, were not adjusted. Median astigmatism for the non-adjusted group was 3.00 DC and for the entire group was 2.88 DC. Long-term refraction and suture status were monitored with time. Mean follow-up was 112 weeks (range 53-170 weeks). Over the study period the entire group showed significant 'long-term astigmatic drift' (LTAD), from 2.88 DC to 3.25 DC (median drift, 1.25 DC; range, 0.00-5.50 DC) (p < 0.001). Suture adjustment and suture removal showed no significant effect on LTAD. With suture removal between 32 and 84 weeks median LTAD was 1.50 DC. For suture removal after 84 weeks, median LTAD was also 1.50 DC, but the range of LTAD was 1.50 DC, compared with a larger range of 5.00 DC in the earlier suture removal group. The technique of single continuous adjustable sutures for penetrating keratoplasty is safe, effective in reducing astigmatism, but may need modification to further enhance long-term refractive stability.

Digital indocyanine-green videoangiography of occult choroidal neovascularization.

BACKGROUND: Occult choroidal neovascularization (CNV) secondary to age-related macular degeneration occurs in the majority of patients with exudative maculopathy. Since occult CNV cannot be imaged clearly by fluorescein angiography, this condition is untreatable. The authors performed digital indocyanine-green videoangiography (ICG-V) on 657 consecutive eyes with occult CNV by fluorescein angiography to determine if this technique could be useful in enhancing the imaging of the neovascularization, and thus increasing treatment eligibility. MATERIALS AND METHODS: Six hundred fifty-seven consecutive eyes with occult CNV were studied. The fluorescein and ICG angiograms were compared, and the percentage of patients potentially eligible for laser therapy based on ICG findings was calculated. RESULTS: Of 413 eyes with occult CNV without pigment epithelial detachments, focal areas of neovascularization were noted in 89 (22%). Overall, 142 (34.3%) eyes had lesions that were potentially treatable by laser photocoagulation based on additional information provided by ICG-V. Of the 235 eyes with occult CNV and vascularized pigment epithelial detachments, 98 (42%) were eligible for laser therapy based on ICG-V findings. The authors calculate that ICG-V enhances the treatment eligibility by approximately one third. CONCLUSIONS: In diagnosing occult CNV, ICG-V is an important adjunctive technique to fluorescein angiography. This technique is especially useful in delineating occult neovascularization, neovascularization with overlying subretinal hemorrhage or serosanguineous fluid, and neovascularization associated with pigment epithelial detachments. The authors currently suggest that ICG-V be performed in eyes in which well-delineated neovascularization cannot be identified by fluorescein angiography. Based on their preliminary study, it can be expected that one in three patients with occult CNV potentially will be eligible for laser photocoagulation based on ICG-V. Further studies are necessary to confirm these findings.

Adverse reactions due to indocyanine green.

BACKGROUND: Although adverse reactions to indocyanine green (ICG) are known to occur, the dye has been used for more than 30 years in tests of cardiac and hepatic function, with a high level of safety. Improved digital video technology has renewed interest in the use of intravenous ICG in ophthalmic imaging. This report describes the authors' experience regarding the safety of ICG for digital angiography and their recommendations for its use in the ophthalmic setting. METHODS: Digital ICG videoangiography was performed in 1226 consecutive patients, and 1923 ICG videoangiography tests were performed. A registry of adverse reactions to ICG was established. Criteria were used to define mild, moderate, and severe adverse reactions, and these data were recorded for every ICG study performed. RESULTS: There were three (0.15%) mild adverse reactions, four (0.2%) moderate reactions, and one (0.05%) severe adverse reaction. There were no deaths. CONCLUSIONS: This study documents the safety of intravenous ICG for use in ophthalmic videoangiography.

Dye enhanced laser photocoagulation in the treatment of a peripapillary subretinal neovascular membrane.

A 45-year-old female with an elevated peripapillary subretinal neovascular membrane was treated with dye enhanced laser photocoagulation, using indocyanine green and the diode laser. Following treatment the membrane regressed, with flattening of the lesion. No side effects occurred and excellent visual acuity was maintained over a 12 month follow-up period.

Recurrent corneal erosion: clinical features.

The clinical features of a group of 30 patients with recalcitrant recurrent corneal erosions (i.e. those who failed to respond to conventional therapy) were evaluated. Associated ocular and facial abnormalities were documented. Meibomian gland dysfunction was present in all patients as manifest by dropout and inspissation of the meibomian glands, reduced tear film break-up time and debris in the tear film. Dropout of meibomian glands was present in 25 (83%) patients and was maximum in the medial half of the lid in 21 (84%) of these 25 patients. Tear film break-up time was reduced in all patients, being instant in 7 (23%), between 1 and 5 seconds in 22 (74%) and between 10 and 15 seconds in 1 (3%) patient. Superficial corneal abnormalities were present in 28 (93%) patients as manifest by maps, dots and fingerprints. Facial abnormalities such as telangiectasia, rhinophyma and acne rosacea were present in 22 (73%) patients. The findings of our study suggest an association between recalcitrant recurrent corneal erosions and meibomian gland dysfunction.

Oral tetracycline in the treatment of recurrent corneal erosions.

We report the results of a prospective, randomised controlled, 24 week trial to assess the efficacy of oral tetracycline and oral tetracycline with topical prednisolone in the treatment of recalcitrant recurrent corneal erosions, i.e. those which fail to respond to standard therapy. A total of 30 patients were randomly allocated to either standard treatment (group A), standard treatment and oral tetracycline (group B) or standard treatment, oral tetracycline and topical prednisolone (group C). Treatment groups B and C were instructed to perform daily lid hygiene. There was a significant reduction in the number of recurrent corneal erosions during the 24 week study period in group B (p = 0.04) and in group C (p = 0.0003) but not in group A (p = 0.66). There was a significant difference in the accelerated healing time of recurrent corneal microerosions between groups A and B (p = 0.001) and between groups A and C (p = 0.001). There was a significant improvement in the symptom scores during the study in treatment groups B and C (p = 0.005) but not in group A (p = 0.15). We conclude that lid hygiene and oral oxytetracycline 250 mg twice daily for 12 weeks with or without topical prednisolone for the first 7 days is beneficial in the management of recalcitrant recurrent corneal erosions.

Detection of varicella-zoster virus DNA in ocular samples from patients with uveitis but no cutaneous eruption.

Herpes zoster ophthalmicus is a well-recognised cause of intraocular inflammation, which may become recurrent or chronic after the acute phase has elapsed. Although it commonly presents with the typical rash, cases of ocular zoster with no cutaneous eruption have been well documented. We present two patients with unilateral anterior uveitis complicated by cataract, in whom molecular techniques based on the polymerase chain reaction detected varicella-zoster virus DNA in intraocular material obtained during cataract surgery. Neither patient gave a history of cutaneous eruption.