Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines.

AIM: This systematic review aimed to provide an overview of (inter)national guidelines on the treatment of peritoneal metastases of colorectal cancer origin (PMCRC) and to determine the degree of consensus and available evidence with identification of topics for future research. METHOD: A systematic search of MEDLINE, Embase, PubMed as well as Tripdatabase, National Guideline Clearinghouse, BMJ Best Practice and Guidelines International Network was performed to identify (inter)national guidelines and consensus statements from oncological or surgical societies on PMCRC. The quality of guidelines was assessed using the AGREE-II score. Topics followed by recommendations were extracted from the guidelines. The recommendations, highest level of supporting evidence and the degree of consensus were determined for each topic. RESULTS: Twenty-one guidelines were included, in most (15) of which cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) was recommended in selected patients based on level 1b evidence. Substantial consensus was also reached on the benefit of multidisciplinary team discussion and the achievability of a (near) complete cytoreduction (CC0-1) without supporting evidence. Both evidence and consensus were lacking regarding other aspects including preoperative positron emission tomography/CT, second look surgery in high risk patients, the optimal patient selection for CRS/HIPEC, procedural aspects of HIPEC and (perioperative) systemic therapy. CONCLUSION: In currently available guidelines, evidence and consensus on the treatment strategy for PMCRC are lacking. Updates of guidelines are ongoing and future (randomized) clinical trials should contribute to multidisciplinary and international consensus on treatment strategies for PMCRC.

Organ preservation in rectal cancer: a synopsis of current guidelines.

BACKGROUND: The high morbidity associated with radical resection for rectal cancer is an incentive for surgeons to adopt strategies aimed at organ preservation, particularly for early disease. There are a number of different approaches to achieve this. In this study we have collated current national and international guidelines to produce a synopsis to support this changing practice. METHODS: The databases PubMed, Embase, Trip database, national guideline clearinghouse, BMJ Best practice were interrogated. Guidelines published before 2010 were excluded. The AGREE-II tool was used for quality assessment. RESULTS: 24 guidelines were drawn from 2278 potential publications. A consensus exists for local excision for "low risk" T1 rectal cancer but there is no agreement how to stratify the risk of treatment failure. There is a low level of agreement for rectal preservation for more advanced disease but when mentioned is recommended for unfit patients or in th context of a clinical trial. Guidelines are inconsistent with respect to surveillance in node negative disease and after, complete response to chemoradiotherapy CONCLUSION: According to current guidelines and consensus statements organ preservation for rectal cancer beyond low risk T1, is still considered experimental and only indicated in patients unsuitable for radical surgery.. Follow up strategies and cN0 staging deserve attention and highlight the need for high quality clinical trials. This article is protected by copyright. All rights reserved.

Empowering patients with high myopia: The significance of education.

PURPOSE: To investigate the status of patient education among highly myopic individuals focusing on the presence, sources, content, timing of the education and impact on patients. METHODS: Self-reported data were collected through an online 13-item questionnaire consisting of open and multiple-choice questions. The questionnaire was sent to 250 highly myopic members of a patient organization in the Netherlands, of whom 128 (51%) responded. RESULTS: At least one acute event had occurred in 66% (84/128) of participants at the time of the questionnaire. Among all participants, 25% (32/128) had not received patient education regarding alarm symptoms for any of these events. Among those who had been informed, the ophthalmologist was the most frequent (57%, 73/128) source of information. Participants who visited the ophthalmologist annually were more frequently informed than participants without annual visits (53%, 26/49 versus 26%, 9/35, p = 0.002). Those not informed were more likely to have a more than 3 days patient delay (92%, 12/13). Doctors delay was also present; 26% (22/84) of the participants with alarm symptoms had to wait 2 or more days before the first appointment. Long-term consequences of myopia had been discussed with 102 participants (80%, 102/128), again with the ophthalmologist as the most frequent source (59%, 76/128). PERSPECTIVES: Many myopic individuals have not been educated about their increased risk of acute events, which can result in patient delay and serious consequences with respect to visual prognosis. These findings underscore the critical importance of integrating patient education across the entire ophthalmic care chain for myopia.

Sex steroids and markers of micro- and macrovascular damage among women and men from the general population.

AIMS: The contribution of sex hormones to micro- and macrovascular damage might differ among women and men. In particular, little is known about the association between sex hormones and small vessel disease. Therefore, we examined the association of total oestradiol, total testosterone, free-androgen index (FAI), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione levels with micro- and macrovascular diseases. METHODS AND RESULTS: This cross-sectional study included 2950 women and 2495 men from the population-based Rotterdam Study. As proxy of microvascular damage, we measured diameters of retinal arterioles and venules. Markers of macrovascular damage included carotid intima-media thickness and carotid plaque, coronary artery calcification (CAC), and peripheral artery disease. Linear and logistic regression models were used and adjusted for age, cardiovascular risk factors, and years since menopause. Associations with microvasculature: In women, total testosterone [mean difference per 1-unit increase in natural-log transformed total testosterone (95% confidence interval, CI): 2.59 (0.08-5.09)] and androstenedione [4.88 (1.82-7.95)] and in men DHEAS [2.80 (0.23-5.37)] and androstenedione [5.83 (2.19-9.46)] were associated with larger venular caliber. Associations with markers of large vessel disease: In women, higher total testosterone [-0.29 (-0.56 to -0.03)], FAI [-0.33 (-0.56 to -0.10)], and androstenedione levels [-0.33 (-0.64 to -0.02)] were associated with lower CAC burden and FAI [odds ratio (95% CI): 0.82 (0.71-0.94)] was associated with lower prevalence of plaque. CONCLUSION: A more androgenic profile was associated with more microvascular damage in both women and men. Among women, however, higher androgen levels were also associated with less macrovascular damage. Our findings suggest that androgens might have distinct effects on the vasculature, depending on the vascular bed and stages of the atherosclerosis process.

Metachronous peritoneal metastases in patients with pT4b colon cancer: An international multicenter analysis of intraperitoneal versus retroperitoneal tumor invasion.

BACKGROUND: It was hypothesized that colon cancer with only retroperitoneal invasion is associated with a low risk of peritoneal dissemination. This study aimed to compare the risk of metachronous peritoneal metastases (mPM) between intraperitoneal and retroperitoneal invasion. METHODS: In this international, multicenter cohort study, patients with pT4bN0-2M0 colon cancer who underwent curative surgery were categorized as having intraperitoneal invasion (e.g. bladder, small bowel, stomach, omentum, liver, abdominal wall) or retroperitoneal invasion only (e.g. ureter, pancreas, psoas muscle, Gerota's fascia). Primary outcome was 5-year mPM cumulative rate, assessed by Kaplan-Meier analysis. RESULTS: Out of 907 patients with pT4N0-2M0 colon cancer, 198 had a documented pT4b category, comprising 170 patients with intraperitoneal invasion only, 12 with combined intra- and retroperitoneal invasion, and 16 patients with retroperitoneal invasion only. At baseline, only R1 resection rate significantly differed: 4/16 for retroperitoneal invasion only versus 8/172 for intra- +/- retroperitoneal invasion (p = 0.010). Overall, 22 patients developed mPM during a median follow-up of 45 months. Two patients with only retroperitoneal invasion developed mPM, both following R1 resection. The overall 5-year mPM cumulative rate was 13% for any intraperitoneal invasion and 14% for retroperitoneal invasion only (Log Rank, p = 0.878), which was 13% and 0%, respectively, in patients who had an R0 resection (Log Rank, p = 0.235). CONCLUSION: This study suggests that pT4b colon cancer patients with only retroperitoneal invasion who undergo an R0 resection have a negligible risk of mPM, but this is difficult to prove because of its rarity. This observation might have implications regarding individualized follow-up.

Curative-intent surgery for isolated locoregional recurrence of colon cancer: Review of the literature and institutional experience.

BACKGROUND: Locoregional recurrence of colon cancer (LRCC) following curative resection is an underreported clinical entity, especially regarding isolated LRCC which is amenable for surgery. The purpose of this study was to review the literature on incidence of LRCC and surgical treatment with corresponding outcome, and to describe an institutional experience with curative-intent surgery, whether or not as part of a multimodality approach. METHODS: The PubMed and Medline literature databases 1978-2017 were searched and retrieved articles were assessed for eligibility. Based on a prospectively maintained database since 2010 at a tertiary referral center, original patient files were retrospectively reviewed. RESULTS: Systematic literature review resulted in 11 studies reporting on incidence of LRCC, which ranged from 3.1% to 19.0% before 2010, and from 4.4% to 6.7% in three most recent studies. Twelve identified studies reported on outcome of surgically treated LRCC, with a median survival of 30 and 33 months in the two largest studies. The institutional database entailed 17 patients who underwent resection of isolated LRCC between 2010 and 2018. Median time to recurrence was 19 months. After a median follow-up after resection of LRCC of 20 months, 7 patients had died, 9 patients were alive without evidence of disease and 1 patient with evidence of disease; Median DFS was 36 months and 3-year OS was 65%. CONCLUSION: Locoregional recurrence of colon cancer occurs in about 5% in most recent series, of whom selected patients are eligible for surgical treatment, with a fair chance of long-term disease control.

Effectiveness study of atropine for progressive myopia in Europeans.

PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country.MethodsAn effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy.ResultsMean spherical equivalent at baseline was -6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (-1.0D/year±0.7) diminished substantially during treatment (-0.1D/year±0.7) compared to those who ceased therapy (-0.5D/year±0.6; P=0.03).ConclusionsDespite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans.

[Myopia, a growing health problem]. / Bijziendheid, een groeiend probleem.

- Myopia is the eye disorder with the most rapid increase in prevalence worldwide. It develops in childhood, with a peak incidence between the ages of 13 to 15 years. - Especially high myopia, i.e. a refractive error of -6 diopters or more, increases the risk of permanent visual impairment during adulthood due to structural abnormalities of the retina and optic nerve.- The cause of myopia is complex. Lifestyle factors in childhood, such as limited time spent outdoors and close work - such as reading and smartphone usage - are risk factors. Furthermore, genetic studies have revealed more than 100 factors associated with the development of myopia. - Pharmacological and optical interventions to inhibit myopia progression are increasingly applied. The use of atropine eye drops in children and has shown to be an effective treatment.

Genes, pathways, and animal models in primary open-angle glaucoma.

Glaucoma is an optic neuropathy characterized by loss of retinal ganglion cells (RGCs) and consequently visual field loss. It is a complex and heterogeneous disease in which both environmental and genetic factors play a role. With the advent of genome-wide association studies (GWASs), the number of loci associated with primary open-angle glaucoma (POAG) have increased greatly. There has also been major progress in understanding the genes determining the vertical cup-disc ratio (VCDR), disc area (DA), cup area (CA), intraocular pressure (IOP), and central corneal thickness (CCT). In this review, we will update and summarize the genetic loci associated so far with POAG, VCDR, DA, CA, IOP, and CCT. We will describe the pathways revealed and supported by genetic association studies, integrating current knowledge from human and experimental data. Finally, we will discuss approaches for functional genomics and clinical translation.

Incidence and progression rates of age-related maculopathy: the Rotterdam Study.

PURPOSE: To describe the incidence rate of age-related macular degeneration (AMD) and the progression rates of early stages of age-related maculopathy (ARM), and to study the hierarchy of fundus features that determine progression. METHODS: A group of 4953 subjects aged 55 years and older living in Rotterdam, The Netherlands, was studied at baseline and at 2-year follow-up to determine the incidence of neovascular and atrophic AMD. A subgroup of 1244 subjects was studied for progression of early stages of ARM. Fundus transparencies were graded for features of ARM using the International Classification System. ARM was stratified in four exclusive stages, according to type of drusen and presence of pigmentary irregularities. RESULTS: The overall 2-year cumulative incidence of AMD was 0.2%, increasing to 1.8% in subjects of 85 years and older. Of those in the early stages, one fourth showed progression to a more severe stage. The most important predictors for progression were more than 10% of macular area covered by drusen (odds ratio [OR] 5.7, 95% confidence interval [CI] 2.9-11.3), presence of depigmentation (OR 4.0, 95% CI 2.5-6.4), and hyperpigmentation (OR 3.4, 95% CI 2.1-5.4). CONCLUSIONS: The incidence of AMD appears to be lower in The Netherlands than in the United States. Progression of early ARM stages occurs in a distinct pattern at a stable rate, with a large area of drusen and presence of pigmentary changes as the most important predictors.

Changing views on open-angle glaucoma: definitions and prevalences--The Rotterdam Study.

PURPOSE: To create a quantitative basis for diagnostic criteria for open-angle glaucoma (OAG), to propose an epidemiologic definition for OAG based on these, and to determine the prevalence of OAG in a general white population. METHODS: Of the 7983 subjects 55 years of age or older participating in the population-based Rotterdam Study, 6756 subjects participated in the ophthalmic part of this study (6281 subjects living independently and 475 in nursing homes). The criteria for the diagnosis of OAG were based on ophthalmoscopic and semiautomated Imagenet estimations of the optic disc such as vertical cup-to-disc ratio (VCDR), minimal width of neural rim, or asymmetry in VCDR between both eyes, and visual field testing with kinetic Goldmann perimetry. All criteria for the diagnosis of OAG were assessed in a masked way independently of each other. RESULTS: Mean VCDR on ophthalmoscopy was 0.3 and with Imagenet 0.49, and the 97.5th percentile for both was 0.7. The prevalence of glaucomatous visual field defects was 1.5%. Overall prevalence of definite OAG in the independently living subjects was 0.8% (95% confidence interval [CI] 0.6, 1.0; 50 cases). Prevalence of OAG in men was double that in women (odds ratio 2.1; 95% CI 1.2, 3.6). Different commonly used criteria for diagnosis of OAG resulted in prevalence figures ranging from 0.1% to 1.2%. CONCLUSIONS: The overall prevalence of OAG in the present study was comparable to most population-based studies. However, prevalence figures differed by a factor of 12 when their criteria for OAG were applied to this population. A definition for definite OAG is proposed: a glaucomatous optic neuropathy in eyes with open angles in the absence of history or signs of secondary glaucoma characterized by glaucomatous changes based on the 97.5 percentile for this population together with glaucomatous visual field loss. In the absence of the latter or of a visual field test, it is proposed to speak of probable OAG based on the 99.5th or possible OAG based on the 97.5th percentiles of glaucomatous disc changes for a population under study.

The genetics of age-related macular degeneration.

Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

Pigmentary irregularities and optic disc edema after heart transplantation.

OBJECTIVES: To determine the prevalence of chorioretinal lesions and optic disc edema after heart transplantation and to study potential associations. DESIGN AND PATIENTS: One hundred one patients who had undergone heart transplantation at one institution and 19 patients prior to heart transplantation underwent ophthalmological examination, including fundus photography. The prevalence of fundus lesions was then compared between the two groups. MAIN OUTCOME MEASURE: With a standardized protocol, the presence of optic disc edema, chorioretinal hyperpigmentation and depigmentation, retinal hemorrhages, cotton-wool lesions, and arteriovenous nicking was graded on color transparencies. RESULTS: The prevalence of optic disc edema and hypopigmentations was significantly higher among the transplant recipients than among the patients prior to heart transplantation (31% vs 5%, P = .01, and 55% vs 11%, P < .001, respectively). Hyperpigmentation was only present in patients after transplantation (15% vs 0%, P = .06). Heart transplant recipients showed an increased risk of hyperpigmentations after 2.5 years. Acute rejection episodes were not associated with posterior pole lesions. CONCLUSION: Common posterior pole lesions after heart transplantation are optic disc edema and pigmentary changes. Although visual acuity does not seem severely impaired, further longitudinal study is necessary to evaluate the long-term significance of these lesions.

Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study.

OBJECTIVE: To study the prevalence and causes of blindness and visual impairment in various age categories of a large population-based study. METHODS: For the study, 6775 subjects aged 55 years or older underwent an extensive ophthalmologic screening examination, including measurements of visual acuity and the visual field and fundus photography. The causes of blindness or visual impairment were determined using all screening information and medical records. RESULTS: The prevalence of blindness, according to World Health Organization criteria, ranged from 0.1% in subjects aged 55 to 64 years to 3.9% in subjects aged 85 years or older; the prevalence of visual impairment ranged from 0.1% to 11.8%. For persons younger than 75 years, myopic degeneration and optic neuropathy were the most important causes of impaired vision. For persons aged 75 years or older, age-related macular degeneration was the major cause of the increased prevalence of blindness, whereas age-related cataract predominantly caused the increased prevalence of visual impairment. CONCLUSIONS: The hierarchy of causes of blindness and visual impairment is highly determined by age. As yet, little can be done to reduce the exponential increase of blindness; however, adequate implementation of surgery to treat cataract could reduce visual impairment by one third. Underuse of ophthalmologic care is a prominent cause of the high frequency of untreated cataracts among the elderly.

Genetic risk of primary open-angle glaucoma. Population-based familial aggregation study.

OBJECTIVES: To study familial aggregation of primary open-angle glaucoma in a general population and to determine the absolute and relative risks for first-degree relatives. METHODS: First-degree relatives of patients with glaucoma (n = 48) and control subjects (n = 155) from the population-based Rotterdam Study underwent a standardized examination, including perimetry. MAIN OUTCOME MEASURES: Intraocular pressure, vertical cup-disc ratio; and the presence of glaucoma, defined as a visual field defect with a cup-disc ratio of 0.7 or higher or asymmetry of 0.3 or higher between both eyes. RESULTS: The prevalence of glaucoma was 10.4% in siblings of patients, 1.1% in offspring of patients, 0.7% in siblings of controls, and 0% in offspring of controls. Life-time risk of elevated intraocular pressure in relatives of patients vs relatives of controls was 42.5% vs 6.7%, of enlarged cup-disc ratio was 62.2% vs 16.6%, and of glaucoma was 22.0% vs 2.3%, yielding a risk ratio for glaucoma of 9.2 (95% confidence interval = 1.2-73.9). The population-attributable risk of glaucoma was 16.4%. CONCLUSIONS: In a general population, relatives of patients with glaucoma have a strongly increased risk of glaucoma. Enlarged cup-disc ratio, not intraocular pressure, was the earliest and most prominent feature of familial aggregation. Further studies are needed to disentangle the genetic components of the increased familial risk.

Genetic risk of age-related maculopathy. Population-based familial aggregation study.

OBJECTIVE: To investigate to what extent age-related maculopathy (ARM) is genetically determined. DESIGN AND SETTING: Familial aggregation study based on probands derived from the population-based Rotterdam Study. PARTICIPANTS: First-degree relatives of 87 patients with late ARM, i.e., atrophic or neovascular macular degeneration, were compared with first-degree relatives of 135 control subjects without ARM. MAIN OUTCOME MEASURES: Presence and stage of ARM as diagnosed on fundus transparencies, odds ratio, lifetime risk, risk ratio, and population-attributable risk. RESULTS: Independent of other risk factors, the prevalence of early (odds ratio = 4.8, 95% confidence interval [CI] = 1.8-12.2) and late (odds ratio = 19.8, 95% CI = 3.1-126.0) ARM was significantly higher in relatives of patients with late ARM. The lifetime risk estimate of late ARM was 50% (95% CI = 26%-73%) for relatives of patients vs 12% (95% CI = 2%-16%) for relatives of controls (P < .001), yielding a risk ratio of 4.2 (95% CI = 2.6-6.8). Relatives of patients expressed the various features of ARM at a younger age. The population-attributable risk related to genetic factors was 23%. CONCLUSIONS: First-degree relatives of patients with late ARM developed ARM at an increased rate at a relatively young age. Our findings indicate that approximately one fourth of all late ARM is genetically determined and suggest that genetic susceptibility may play an important role in determining the onset of disease.

An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.

A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.

Distribution of central corneal thickness and its association with intraocular pressure: The Rotterdam Study.

PURPOSE: To perform a cross-sectional study on the distribution of central corneal thickness and its association with intraocular pressure in an elderly population. METHODS: We measured central corneal thickness and intraocular pressure in 395 subjects (352 control subjects, 13 patients with ocular hypertension, and 30 patients with primary open-angle glaucoma) aged 55 years or more. RESULTS: Mean central corneal thickness in the 352 control subjects was 537.4 microm (95% confidence interval [CI], 533.8 to 540.9 microm; range, 427 to 620 microm), with a maximal difference between eyes of 42 microm. There were no differences between sexes and no significant association with age. Linear regression analysis showed an increase of 0.19 mm Hg in intraocular pressure with each 10-microm increase in central corneal thickness (95% CI, 0.09 to 0.28 mm Hg). This association was similar in both eyes and in both sexes. The 13 patients with ocular hypertension had corneas a mean of 16.0 microm thicker (95% CI, -2.6 to +34.6 microm) compared with control subjects (P = .093); the 30 patients with primary open-angle glaucoma had corneas a mean of 21.5 microm thinner (95% CI, 8.8 to 34.1 microm) compared with control subjects (P = .001). CONCLUSION: Mean central corneal thickness was similar to that found in clinical studies, was slightly higher in patients with ocular hypertension, and was significantly lower in patients with primary open-angle glaucoma. Intraocular pressure was positively related with central corneal thickness. Central corneal thickness may influence the division between normal and increased intraocular pressure at a simple cutoff point of 21 mm Hg.

Evaluation of the ARMD1 locus on 1q25-31 in patients with age-related maculopathy: genetic variation in laminin genes and in exon 104 of HEMICENTIN-1.

The age-related maculopathy (ARM) genetics program at Columbia University utilizes comprehensive genetic analysis of candidate genes in large case-control studies to determine genotypes associated with the ARM complex trait. Genes encoding laminins, a class of extracellular matrix proteins, represent attractive candidates for two reasons. First, the presence of laminins in the basal lamina of the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris suggests a possible role in the pathophysiology of ARM. Second, three laminin genes, LAMC1, LAMC2, and LAMB3, are located in the 1q25-31 region, within the previously mapped ARMD1 locus. The entire open reading frame of the three laminin genes was screened for variants by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing in at least 92, and up to 368 ARM patients and matched unaffected controls. Sixty-nine sequence variants were detected in the 69 exons of the LAMC1, LAMC2, and LAMB3 genes. Screening of exon 104 of the recently proposed ARMD1 gene, HEMICENTIN-1, residing in the 1q25-31 locus, did not detect the suggested causal variant, Q5345R, in 632 study subjects. Overall, we did not find statistically significant differences in the frequency of variants between ARM-affected individuals and age-matched controls. Four rare, non-synonymous, variants were detected in single cases of ARM patients. Our data on relatively limited numbers of study subjects do not suggest a significant role for genetic variation in the three laminin genes and in exon 104 of HEMICENTIN-1 in predisposing individuals to ARM. However, as in many instances in similar studies, involvement of rare amino acid-changing variants in a fraction of ARM cannot be ruled out.