Leonoor I. Los

Idiopathic epiretinal membrane

Background: Idiopathic epiretinal membrane (iERM) is a fibrocellular membrane that proliferates on the inner surface of the retina at the macular area. Membrane contraction is an important sight-threatening event and is due to fibrotic remodeling. Methods: Analysis of the current literature regarding the epidemiology, clinical features, and pathogenesis of iERM and fibrotic tissue contraction. Results: Epidemiologic studies report a relationship between iERM prevalence, increasing age, and posterior vitreous detachment. Clinically, iERM progresses through different stages characterized by an increased thickness and wrinkling of the membrane. Pathophysiologically, iERM formation is a fibrotic process in which myofibroblast formation and the deposition of newly formed collagens play key roles. Anomalous posterior vitreous detachment may be a key event initiating the formation of iERM. The age-related accumulation of advanced glycation end products may contribute to anomalous posterior vitreous detachment formation and may also influence the mechanical properties of the iERM. Conclusion: Remodeling of the extracellular matrix at the vitreoretinal interface by aging and fibrotic changes, plays a significant role in the pathogenesis of iERM. A better understanding of molecular mechanisms underlying this process may eventually lead to the development of effective and nonsurgical approaches to treat and prevent vitreoretinal fibrotic diseases.

Remodelling of the human vitreous and vitreoretinal interface - A dynamic process

The highly hydrated, almost acellular vitreous body of the human eye consists of only 0.1% macromolecules, of which collagens are the most important for its matrix structure. During embryological development, the human vitreous body is a highly dynamic matrix, in which the primary (vascular) vitreous is gradually replaced by the secondary (avascular) vitreous. With aging, the human vitreous undergoes a slowly progressive remodelling, characterized by the gradual formation of collagenous condensations and liquefied spaces in the gel structure. The former is probably the result of collagen synthesis and the deposition of newly formed collagen into the matrix, while the latter is probably due to collagen breakdown. Therefore, remodelling of the vitreous matrix starts at a very early age and continues into old age, albeit at a slower pace. Older theories and concepts of a strict spatial separation between the primary and secondary vitreous during embryonic development, and morphological changes in the aging vitreous being due to a simple aggregation of collagen fibrils are questioned. This review describes the embryological and postnatal remodelling of the human vitreous matrix and vitreoretinal interface, in addition to the mechanisms and cells that are potentially involved in this process.

Collagen Distribution in the Human Vitreoretinal Interface

PURPOSE To evaluate the presence of collagen types I to VII, IX, XI, and XVIII at the posterior pole, the equator and the pre-equatorial area in human donor eyes, since collagens are important macromolecules that contribute to vitreoretinal adhesion at the vitreoretinal interface. METHODS Freshly isolated human retinectomy samples from the equator were used for reverse transcription-polymerase chain reaction to detect mRNA of the above-mentioned collagens. In addition, human donor eyes and equatorial retinectomy samples were embedded in paraffin, stained with antibodies against the collagens and evaluated by light microscopy (LM). RESULTS Retinectomy samples expressed mRNA of all tested collagen types. By LM, vitreous cortex was positive for collagen types II, V, IX, and XI. In all three regions within the donor eyes and in the retinectomy samples, the internal limiting membrane (ILM) showed types IV, VI, and XVIII; the retinal vasculature was positive for types I to VI and XVIII in most specimens; and the retinal layers showed condensed spots of type VII. In addition, type VII increased in density and in distribution over the retinal layers toward the posterior pole. CONCLUSIONS Staining patterns of collagen types I to V, IX, XI, and XVIII confirmed previous observations. Important new findings include the presence of type VI in the ILM and type VII in several layers of the retina. Both collagens can anchor matrix components, and type VI could be involved in vitreoretinal attachment. Furthermore, the presence of collagen mRNA in human retinectomy samples may be an indication of postnatal collagen production by retinal cells.

Refractive surgery for high myopia

Surgical correction of high myopia is indicated in a limited number of cases. Techniques include (epi)keratophakia, keratomileusis and implantation of a negative-power IOL. The iris claw lens, fixed to the midperiphery of the iris, has proved its safety in aphakic eyes. The model has been adapted by giving it a vault in order to make it suitable for implantation in high myopic phakic eyes. The implantation technique and short-term results of patients operated by Worst are presented.

The Incidence of Rhegmatogenous Retinal Detachment in The Netherlands

OBJECTIVE To estimate the incidence and characteristics of rhegmatogenous retinal detachment (RRD) in The Netherlands in 2009. DESIGN Retrospective, observational case series. PARTICIPANTS All patients with RRD in the Dutch population in 2009. METHODS By reviewing surgical logs, cases of primary RRD repair in 2009 were identified. Exclusion criteria included RRD before 2009 and exudative, tractional, or traumatic retinal detachments. Patient demographics, date of surgery, and lens status were documented. Incidence of RRD and 95% confidence intervals (CIs) were calculated based on the Poisson distribution. Age distribution, male-to-female ratio, and proportion of RRD patients with prior cataract extraction (CE) were determined. A Student t test was used to examine differences in the incidence of RRD between groups. MAIN OUTCOME MEASURES Annual RRD incidence in the population and per gender-adjusted age category and proportion of RRD patients with prior CE. RESULTS The annual RRD incidence was 18.2 per 100 000 people (95% CI, 11.4-18.8), with a peak incidence of 52.5 per 100 000 people (95% CI, 29.4-56.8) between 55 and 59 years of age. The Bilateral RRD rate was 1.67%. Macula-off presentation occurred in 54.5% of all RRD patients. Prior CE was noted in 33.5% of RRD eyes. The male-to-female ratio was 1.3:1, and RRD incidence was statistically significantly more frequent in males (P<0.0001). CONCLUSIONS Rhegmatogenous retinal detachment is predominantly a disease of the population older than 50 years, and males are more susceptible to RRD. The annual RRD incidence is highly dependent on demographic characteristics.

The clinical course of juvenile idiopathic arthritis-associated uveitis in childhood and puberty

Aim The long-term course of juvenile idiopathic arthritis (JIA)-associated uveitis is not known yet. This study investigates the course and activity of JIA-associated uveitis in childhood and puberty. Design Retrospective study of the clinical data of 62 JIA patients with uveitis. The main outcome measurements consisted of uveitis activity measured as mean cell grade in the anterior chamber, topical and systemic medication and ocular complications related to disease activity. All data were scored and evaluated per year of age. Results Uveitis activity took a biphasic course with a quiet phase around the age of 9 years and showed increased activity during early teenage years. The biphasic course was significantly related to age (p=0.048) but not to uveitis duration. More patients were treated with systemic immunosuppressive medication in estimated puberty years (63% in boys, 53% in girls) compared with prepuberty years (46% and 28%, respectively), although the difference was only significant in girls (p<0.001). The presence of cystoid macular oedema and papillitis was not significantly related to estimated puberty, but the development of an hypotonous eye was more frequently observed in boys in estimated puberty years (p=0.026). Conclusions JIA-associated uveitis appears to take a biphasic course with the second phase of activity during early teenage years and more treatment with systemic immunosuppressive medication occurred during estimated puberty compared with prepuberty years.

Visual Outcome, Treatment Results, and Prognostic Factors in Patients with Scleritis

PURPOSE To analyze the visual outcome, systemic associations, effectiveness of treatment, and predicting features of 104 scleritis patients. DESIGN Retrospective case series. PARTICIPANTS One hundred four patients treated for scleritis at the University Medical Centers of Groningen and Utrecht, The Netherlands. METHODS The clinical records of 104 patients diagnosed with scleritis between 1992 and 2011 at the University Medical Centers of Groningen (n = 64) and of Utrecht (n = 40) were analyzed retrospectively. MAIN OUTCOME MEASURES Loss of visual acuity, ocular complications, related systemic disease, type of treatment, time to treatment success, and predictive features. RESULTS Mean age ± standard deviation (SD) was 51.5 ± 13.6 years, and 63 (60.6 %) patients were female. Mean follow-up ± SD was 38.2 ± 33.8 months. A loss of more than 2 lines of Snellen acuity was observed in 23 patients, 3 of whom had a final visual acuity of no light perception. In general, patients with necrotizing scleritis (n = 15) had a poorer outcome. Ocular complications were observed in 88 (84.6%) patients. Underlying systemic disease was identified in 34 (32.7%) patients. Steroid-sparing immunosuppressive medication was used in 47 patients, 36 of whom were treated with methotrexate (MTX). This treatment was successful in 17 (47.2%) patients over the course of a mean ± SD of 103.7 ± 83.7 weeks. Mycophenolate mofetil was the treatment in 10 patients, and in 5 of these patients, treatment success was achieved in a mean ± SD of 65.3 ± 37.4 weeks. Treatment with tumor necrosis factor α (TNF-α) antagonists led to treatment success in a mean ± SD of 32.6 ± 21.8 weeks in 5 of the 11 treated patients. Patients with loss of visual acuity or those treated with steroid-sparing immunosuppressive drugs more often had an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation. CONCLUSIONS Scleritis is a severe ocular inflammatory disease often associated with ocular complications. In this population, roughly half of the patients were treated with systemic immunosuppressive medication. Mycophenolate mofetil and TNF-α antagonists can be used in case of MTX failure. Tumor necrosis factor α antagonists seemed to be more effective than MTX. Within this group, an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation were predictive features for a more severe disease course.

Intraocular degradation behavior of crosslinked and linear poly(trimethylene carbonate) and poly(d,l-lactic acid)

The intraocular degradation behavior of poly(trimethylene carbonate) (PTMC) networks and poly(D,L-lactic acid) (PDLLA) networks and of linear high molecular weight PTMC and PDLLA was evaluated. PTMC is known to degrade by enzymatic surface erosion in vivo, whereas PDLLA degrades by hydrolytic bulk degradation. Rod shaped specimens were implanted in the vitreous of New Zealand white rabbits for 6 or 13 wk. All materials were well tolerated in the rabbit vitreous. The degradation of linear high molecular weight PTMC and PTMC networks was very slow and no significant mass loss was observed within 13 wk. Only some minor signs of macrophage mediated erosion were found. The fact that no significant enzymatic surface erosion occurs can be related to the avascularity of the vitreous and the limited number of cells it contains. PDLLA samples showed more evident signs of degradation. For linear PDLLA significant swelling and a large decrease in molecular weight in time was observed and PDLLA network implants started to lose mass within 13 wk. Of the tested materials, PDLLA networks seem to be most promising for long term degradation controlled intravitreal drug delivery since this material degrades without significant swelling. Furthermore the preparation method of these networks allows easy and efficient incorporation of drugs.

Pentosidine accumulates in the aging vitreous body: A gender effect

The human vitreous body undergoes structural changes with aging. This can be followed by a posterior vitreous detachment, which can result in ocular pathology. As in many collagenous tissues, age-related changes in the vitreous could be caused by the formation of advanced glycation end products (AGEs). The goal of this study was to find out whether the AGE pentosidine accumulates in the human vitreous with aging. With this data we were able to estimate the half-life of vitreous collagen. Furthermore, we analyzed whether there was a gender difference in pentosidine accumulation, as this was seen in other tissues as well. Using high performance liquid chromatography, pentosidine contents were determined in whole vitreous bodies and in separate parts of vitreous bodies, which were all obtained from human donor eyes. Our results show that pentosidine accumulates in the human vitreous. From the rate of accumulation we could roughly estimate that vitreous collagen has as a similar or shorter half-life compared to skin collagen. This supports the concept of collagen turnover in the vitreous. In general, the female vitreous experiences a faster pentosidine accumulation than the male vitreous, and most of the pentosidine accumulation in the former occurs after 50 years of age.

Long-term ocular complications in aphakic versus pseudophakic eyes of children with juvenile idiopathic arthritis-associated uveitis

Aim To evaluate the long-term follow-up of aphakic and pseudophakic eyes of children with juvenile idiopathic arthritis (JIA)-associated uveitis with a special interest in whether intraocular lens implantation increases the risk of developing ocular complications. Methods Data were obtained from the medical records of 29 children (48 eyes) with JIA-associated uveitis operated on for cataract before the age of 16 years from January 1990 up to and including March 2007. Main outcome measures were long-term postsurgical complications and visual acuity in aphakic and pseudophakic eyes of children with JIA-associated uveitis. Results The number of complications after cataract extraction including new onset of ocular hypertension and secondary glaucoma, cystoid macular oedema and optic disc swelling did not differ between aphakic and pseudophakic eyes. Moreover, no hypotony, perilenticular membranes and phthisis were encountered in the pseudophakic group. Better visual acuity was observed in the pseudophakic eyes up to and including 7 years of follow-up (p=0.012 at 7 years of follow-up). No differences in the preoperative or adjuvant perioperative treatment with periocular or systemic corticosteroids were found between the two groups; however, significantly more children were treated with methotrexate in the pseudophakic group (p=0.006). Conclusion With maximum control of perioperative inflammation and intensive follow-up, the implantation of an intraocular lens in well-selected eyes of children with JIA-associated uveitis is not associated with an increased risk of ocular hypertension, secondary glaucoma, cystoid macular oedema and optic disc swelling and showed better visual results up to and including 7 years after cataract extraction.