Effect of the duration of immunomodulatory therapy on the clinical features of recurrent episodes in Vogt–Koyanagi–Harada disease

Purpose: To evaluate the duration of immunomodulatory therapy (corticosteroids, immunosuppressive drugs) with regard to the rate of relapses and clinical features (exudative retinal detachment or anterior uveitis) in inflammatory episodes of Vogt–Koyanagi–Harada disease. Methods: Data of all 42 patients diagnosed with acute uveitis associated with VKH disease during the period of January 2005 to December 2008 at the Pitié‐Salpêtrière Hospital or at the Lariboisière Hospital in Paris, France were extracted by chart review. Results: There were 31 patients (73.8%) with episodes of recurrence and were included in the study. At the first recurrence, 81% (13 patients) of exudative retinal detachments (ERD) were associated with an initial immunomodulatory treatment conducted ≤6 months (3.76 months ± 2.67). Conversely, an initial treatment duration of >6 months was associated with anterior uveitis signs for 66% of patients (eight patients) with anterior first recurrence (p = 0.0061). On second episode of recurrence, 75% of patients (three patients) who developed exudative retinal detachment had been managed by immunomodulatory therapy for ≤6 months with the total duration of immunomodulatory treatment ≤6 months during previous inflammatory episodes. Conversely, all 16 patients who presented anterior uveitis with additional manifestations (optic disc oedema, macular oedema, vitritis and/or ‘Sunset glow’ fundus) have been treated for more than 6 months or treated during the initial occurrence lasting more than 9 months (p = 0.0035). Conclusions: The duration of systemic corticosteroids (and/or immunosuppressive drug therapy) for ≤6 months at first and second recurrence was associated with features of further exudative retinal detachment instead of anterior uveitis in VKH disease.     

Prognostic factors for clinical outcomes in patients with Vogt–Koyanagi–Harada disease treated with high‐dose corticosteroids

Purpose: To determine prognostic factors in patients with Vogt–Koyanagi–Harada (VKH) disease who were treated with high‐dose corticosteroids. Methods: Retrospective analysis of 87 patients (174 eyes). Results: At presentation, there were 53 patients with initial‐onset acute VKH disease and 34 patients with chronic recurrent VKH disease. Chronic recurrent presentation was significantly associated with more severe anterior segment inflammation at presentation as indicated by presence of mutton‐fat keratic precipitates, anterior chamber reaction ≥2+, iris nodules and posterior synechiae (p < 0.001 for all comparisons), less exudative retinal detachment at presentation (p < 0.001), more complications during the follow‐up period (p < 0.001) and a worse visual outcome (p < 0.001). The use of immunomodulatory therapy (cyclosporine and mycophenolate mofetil) as first‐line therapy significantly reduced the development of complications in the whole study group (p = 0.006) and in initial‐onset acute group (p = 0.024) and improved visual outcome in the whole study group (p = 0.004) and in chronic recurrent group (p = 0.024). In the whole study group, final visual acuity of 20/20 was significantly associated with good initial visual acuity of >20/200 [odds ratio = 4.25; 95% Confidence interval (CI) = 1.53–11.89] and age older than 16 years was significantly associated with the development of complications (odds ratio = 3.15; 95% CI = 1.04–9.48). Conclusions: Chronic recurrent VKH disease is significantly associated with more severe anterior segment inflammation and less exudative retinal detachment at presentation, more ocular complications and a worse visual outcome than initial‐onset acute VKH disease. Use of immunomodulatory therapy significantly improved the clinical outcomes.     

Vogt–Koyanagi–Harada syndrome in a Greenlandic Inuit

Purpose: To report a case of Vogt–Koyanagi–Harada syndrome (VKH) in an Inuit. Methods: We carried out a medical evaluation and human leucocyte antigen (HLA) genotyping. Results: A 36‐year‐old male Inuit developed severely decreased vision, intense headache and vertigo over a 3‐week period. Ocular examination revealed panuveitis with bilateral serous retinal detachment and optic nerve head oedema. There was no history of ocular trauma or evidence suggestive of other disease entities. The patient responded well to high‐dose systemic prednisolone. Vitiligo presented late in the course. Conclusions: This case report describes the first published case of VKH in a patient of Inuit ancestry. The patient was homozygous for HLA‐DR4, a genotype previously associated with VKH.     

The outcomes of mycophenolate mofetil therapy combined with systemic corticosteroids in acute uveitis associated with Vogt–Koyanagi–Harada disease

Purpose: To study the effectiveness of mycophenolate mofetil (MMF) as first‐line therapy combined with systemic corticosteroids in acute uveitis associated with Vogt–Koyanagi–Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy or with delayed addition of immunomodulatory therapy. Methods: This prospective study included 19 patients (38 eyes) diagnosed with acute uveitis associated with VKH disease. Results: The mean follow‐up period was 27.0 ± 11.1 months (range 16–54 months). Corticosteroid‐sparing effect was achieved in all patients. The mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.1 ± 1.2 months (range 3–7 months). Ten (53%) patients discontinued treatment without relapse of inflammation. The mean time observed of treatment was 17.3 ± 11.9 months (range 3–41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001). Recurrent inflammation of ≥3 times was reduced significantly (p = 0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group (18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None of the eyes in the corticosteroid + MMF group developed ‘sunset glow fundus’. Conclusions: Addition of MMF as first‐line therapy to corticosteroids in patients with acute uveitis associated with VKH disease leads to significant reduction in recurrences of uveitis and development of late complications and significantly improves visual outcome.     

Negative ERGs in mucopolysaccharidoses (MPS) Hurler–Scheie (I-H/S) and Hurler (I-H)-syndromes

The configuration and progression of the ERG in two children with mucopolysaccharidosis (MPS) I H/S (Hurler-Scheie syndrome) and MPS I H (Hurler syndrome) is described. Physical examination, biochemical analysis, ophthalmic examination and electroretinography were performed. The Hurler-Scheie patient (case 1) showed negative scotopic but normal photopic ERGs, which remained unchanged over 2 years. The Hurler patient (case 2) showed negative scotopic and photopic ERGs which did not alter after bone marrow transplantation (BMT). One year after BMT, further b-wave amplitude reduction had caused the ERGs to become more negative. The electronegative configuration of the ERGs suggests that, in these cases of MPS, the primary retinal abnormality in MPS I may be faulty synaptic transmission from photoreceptors to more proximal elements, deficient bipolar responsivity, or Muller cell disease. Further degradation with time suggests the defect to be progressive with BMT causing little or no improvement. In the Hurler-Scheie syndrome case, the defect appears to spare the cone system and to show little or no progression.     

Mucopolysaccharidoses and the eye

The mucopolysaccharidoses (MPSs) are a group of disorders caused by inherited defects in lysosomal enzymes resulting in widespread intra- and extra-cellular accumulation of glycosaminoglycans. They have been subdivided according to enzyme defect and systemic manifestations and include MPS IH (Hurler), MPS IS (Scheie), MPS IH/S (Hurler/Sheie), MPS II (Hunter), MPS III (Sanfilippo), MPS IV (Morquio), MPS VI (Maroteaux-Lamy), MPS VII (Sly) and MPS IX (Natowicz). The mucopolysaccharidoses have a spectrum of systemic manifestations, including airway and respiratory compromise, skeletal deformities, intellectual and neurological impairment, cardiac abnormalities, and gastrointestinal problems. Ocular manifestations are common in the mucopolysaccharidoses and may result in significant visual impairment. Corneal opacification of varying severity is frequently seen, as well as retinopathy, optic nerve swelling and atrophy, ocular hypertension, and glaucoma. New treatment modalities for the systemic manifestations of the mucopolysaccharidoses include bone marrow transplant and enzyme replacement therapy, and have resulted in an improved prognosis in many cases. This article reviews the systemic and ocular manifestations of the mucopolysaccharidoses, as well as new treatment options, and discusses the ophthalmic management of mucopolysaccharidosis patients.     

Acute electroretinographic changes during Sildenafil (Viagra) treatment for erectile dysfunction*

The authors describe their findings on 12 subjects who were treated with 50 mg of Sildenafil (Viagra) and underwent ERG measurements prior to and 1 hour after ingestion. The Naka–Rushton equation was used to describe the b-wave luminance-response function of the scotopic ERG. Statistically significant differences were noted in the V _max and K values. Sildenafil ingestion resulted in an increase in V _max (higher rod response to light stimuli) and a decrease in K (higher sensitivity).     

Predictors for visual field progression and the effects of treatment with dorzolamide 2% or brinzolamide 1% each added to timolol 0.5% in primary open‐angle glaucoma

Purpose: This study aims to identify progression factors in patients with primary open‐angle glaucoma (POAG), including the effects of treatment with dorzolamide 2% or brinzolamide 1%, each added to timolol 0.5%. Methods: A sample of 161 POAG patients were prospectively randomized to receive either dorzolamide 2% (DT) or brinzolamide 1% (BT) b.i.d., each added to timolol 0.5%, during a 60‐month, evaluator‐masked study. Progression was determined by perimetric criteria. Factors associated with visual field progression were estimated using a conditional Cox hazard model with patient intraclass correlation and were expressed as hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: Predictive baseline factors were lower diastolic blood pressure (DBP), lower mean arterial pressure (MAP), antihypertensive treatment, lower end‐diastolic velocity (EDV) in the ophthalmic artery (OA) and short posterior ciliary artery (SPCA), and a higher resistivity index (RI) in the OA and SPCA. Progression risk decreased by approximately 30% and 20% with each centimetre per second increase of EDV in the OA and SPCA, respectively, from baseline to the last follow‐up visit. Each RI decrease (or increase) of 0.01 unit in the OA or SPCA was associated with an approximate 20% decrease (or increase) in risk for progression. In a multivariate analysis, progression risk was significantly lower in eyes treated with DT (HR = 0.65, 95% CI 0.41–0.90) compared with those treated with BT. Conclusions: Progression increased with lower DBP, lower MAP, antihypertensive medication, lower EDV in the OA and SPCA, and higher RI in the OA and SPCA. The risk for progression in patients treated with DT was half that in patients treated with BT.     

Elevated choroidal blood flow velocity during systemic corticosteroid therapy in Vogt–Koyanagi–Harada disease

Purpose: Laser speckle flowgraphy (LSFG) can be used to non‐invasively visualize the haemodynamics of choroidal circulation and the vascular pattern. The purpose of this study was to examine the ability of LSFG to quantitatively evaluate blood flow velocity at the macula in patients with Vogt–Koyanagi–Harada (VKH) disease before and after systemic corticosteroid therapy. Methods: Prednisolone (200 mg/day) was systemically administered in 10 VKH disease patients with serous retinal detachment at the macular area. The drug was gradually tapered to zero over a 6‐month period. Laser speckle flowgraphy measurements were taken in the 20 eyes of these patients at their initial visit and at 1, 4 and 12 weeks after the onset of therapy. Square blur rate (SBR), a quantitative index of relative blood flow velocity, was calculated using LSFG. Results: Serous retinal detachment resolved within 4 weeks after treatment and visual acuities improved to > 1.0 in almost all cases. There were significant increases in average SBR at the macula at 4 weeks after treatment compared with at 1 week after treatment, and also at 12 weeks after treatment compared with at 4 weeks after treatment. Conclusions: These results suggest that systemic corticosteroid therapy improves inflammation‐related impairment in choroidal blood flow velocity at the macula. Laser speckle flowgraphy can evaluate the effect of systemic corticosteroid therapy by enabling comparisons between measurements of blood flow velocity, which is considered to reflect inflammation activity in the choroid.     

Acta Ophthalmologica: History 1970–88

This is my personal memories concerning the Nordic periodical Acta Ophthalmologica in the period 1970–88. Poul Brændstrup was scientific secretary for Acta 1950–70 and chief editor 1970–75. His many important scientific works and enormous work for Acta is described, but also personal topics are mentioned. Acta meetings in the Danish Ophthalmol Society (DOS) and in the Nordic ophtalmol. Congresses are discussed. A referee‐system is established from 1976, but with political contra scientific motives. Only a few papers arrived to Acta. A catastrophe in 1978 is mentioned. The new secretary Ingelise Truberg did an enormous work for the next ten years. Erik Jørgensen (1928–90) was our printer, and from 1975 our idealistic publisher after Munksgaard. The economy became better and the number of papers of high quality increased. The relationship to the new Nordic periodical Oftalmolog was discussed in 1982.     

Gap junction communication influences intercellular protein distribution in the lens

Lens transparency and high refractive index presumably depend on the appropriate arrangement and distribution of lens proteins among lens fiber cells. Intercellular gap junction channels formed by alpha3 and alpha8 connexins are known to transport small molecules, ions and water, but not proteins, in the lens. Mosaic expression of green fluorescent protein (GFP) in the lens is a useful marker for monitoring macromolecule distribution between fiber cells and for constructing three-dimensional images of living lens cells. In alpha3(-/-) alpha8(-/-) double knockout (DKO) lenses, three-dimensional images of GFP-positive cells demonstrate the changes of epithelial cell surfaces and insufficient elongation of inner fiber cells. Uniform distribution of GFP between inner lens fiber cells is observed in both wild-type and alpha3(-/-) lenses. In contrast, uniform GFP distribution is slightly delayed in alpha8(-/-) lenses and is abolished in DKO lenses. Without endogenous wild-type alpha3 and alpha8 connexins, knock-in alpha3 connexin (expressed under the alpha8 gene promoter) restores the uniform distribution of GFP protein in the lens. Thus, the presence of either alpha3 or alpha8 connexins seems sufficient to support the uniform distribution of GFP between differentiated lens fiber cells. Although the mechanism that drives GFP transport between fiber cells remains unknown, this work reveals that gap junction communication plays a novel role in the regulation of intercellular protein distribution in the lens.     

Diffuse choroidal haemangioma in Sturge–Weber syndrome treated with photodynamic therapy under general anaesthesia

Purpose To report the treatment outcome of photodynamic therapy with verteporfin (PDT) for exudative retinal detachment associated with diffuse choroidal haemangioma in Sturge–Weber syndrome.Methods An interventional case report of a 12-year-old girl with Sturge–Weber syndrome who developed an exudative retinal detachment (visual acuity 20/400) that was treated with PDT under general anaesthesia. PDT was performed according to the standard (macular degeneration) protocol, using three nonoverlapping spots of 4,000 m.Results Subretinal fluid resolved completely over a period of 5 months and visual acuity increased to 20/50. No side effects of the PDT treatment were encountered during 9 months follow-up.Conclusion In our patient PDT with verteporfin effectively resolved the exudative retinal detachment associated with a diffuse choroidal haemangioma. Resolution of subretinal fluid occurred over several months without retreatment. We noted no side effects of the combination PDT and general anaesthesia, nor did we encounter ocular side effects of the treatment.