CKD increases the risk of age-related macular degeneration

Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate < 60 ml/min per 1.73 m(2) based on the Cockcroft-Gault equation) was present in 24% of the population (286 of 1183). The 5-yr incidence of early age-related macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P < 0.0001). Each SD (14.8 ml/min per 1.73 m(2)) decrease in Cockcroft-Gault estimated glomerular filtration rate was associated with a doubling of the adjusted risk for early age-related macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P < 0.0001). In conclusion, persons with chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.     

Gamma knife radiosurgery in the treatment of choroidal neovascularization (wet-type macular degeneration)

We evaluated retrospectively our institutional experience in the treatment of macular degeneration with gamma knife radiosurgery (GKR). Treatment was delivered in a single shot of 12 Gy. Seven patients were treated between March of 1999 and May of 2000. The median duration of follow-up was 2.2 years. The majority of patients maintained stable visual acuity after treatment. Our series indicates that GKR may be useful as a salvage treatment for patients who have failed or are ineligible for other treatments for their macular degeneration. Further studies are needed to better define the role of GKR in the treatment of macular degeneration.     

Freiberg’s Infraction in Identical Twins: A Case Report

Freiberg's infraction is an ostechondrosis of a lesser metatarsal head resulting in degeneration of the metatarsophalangeal joint. Several mechanisms have been suggested in its pathenogenesis. Freiberg first described the entity and believed single impact trauma was the underlying cause. Repetitive biomechanical microtrauma is the most widely accepted etiologic theory. Other factors contributing to its development include aseptic necrosis, ischemia, and a congenital predisposition. We present a case report of Freiberg's infraction occurring in identical twins involving multiple metatarsals in various stages of degeneration. One of the twins was affected unilaterally whereas the other twin was affected bilaterally. Both twins had involvement of the second metatarsal on the same side extremity. The occurrence of Freiberg's infraction in identical twins suggests that an underlying congenital predisposition to the condition may play more of a role than previously considered.     

Disc degeneration and bone density in monozygotic twins discordant for insulin-dependent diabetes mellitus.

The effects of insulin-dependent diabetes mellitus on bone density and connective tissue degeneration have theoretical interest and practical relevance. Several experimental studies in animals have demonstrated the harmful effects of insulin deficiency on connective tissues. However, clinical studies in humans have produced somewhat contradictory results, most likely due to difficulties controlling for general degeneration and factors associated with diabetes. In nine pairs of monozygotic twins discordant for insulin-dependent diabetes mellitus, we compared femoral and lumbar bone mineral density (assessed by dual-energy x-ray absorptiometry) and spinal degeneration (assessed by magnetic resonance imaging). The bone densities were, on average, 0.1-0.3% lower (p = 0.87-0.96) in diabetic patients. However, after controlling for smoking, we found that the bone density in the femoral neck was 2.5% (0.025 g/cm2) lower in diabetic individuals than in their twins (p = 0.09). The five magnetic resonance imaging parameters used to evaluate disc degeneration did not differ between diabetic patients and their twins. In conclusion, our results provide no evidence that insulin-dependent diabetes mellitus has any major effect on bone density or disc degeneration.     

Dosage-dependent reduction of macular pigment optical density in female breast cancer patients receiving tamoxifen adjuvant therapy

It is now increasingly common for breast cancer patients to receive adjuvant tamoxifen therapy for a period of up to 10 years. As survival rate increases, managing tamoxifen ocular toxicities is important for patients' quality of life. Macular pigments in photoreceptor cells protect against free radical damage, which can cause macular degeneration. By reducing macular pigment concentration, tamoxifen may increase the risk of macular degeneration. Here, we compared macular pigment optical density (MPOD) and central macular thickness between breast cancer patients on tamoxifen adjuvant therapy (n = 70), and a control group (n = 72). Multiple regression analysis indicated that MPOD decreases with increasing tamoxifen dosage, up to a threshold of about 20 g, after which MPOD plateaus out. Mean MPOD in the treatment group (mean = 0.40) was significantly lower (p-value = 0.02) compared to the control group (mean = 0.47) for the left eye, and for the right eye (treatment mean = 0.39; control mean = 0.48; p-value = 0.009). No significant difference in mean central macular thickness was found between the treatment and the control group (p-values > 0.4). In the control group, MPOD and central macular thickness showed significant correlation (r∼0.30; p-values < 0.01) for both eyes. However, in the treatment group, loss of significant correlation was observed in the left eye (r = 0.21; p-value = 0.08). The present results show that MPOD decreases non-linearly as a function of tamoxifen dosage, and highlight the potential of tamoxifen to reduce macular pigment concentration through an unknown mechanism that does not depend on macular thinning solely.     

1991 Volvo Award in clinical sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins

The primary objective of this study was to determine whether disc degeneration, as assessed through magnetic resonance imaging, is greater in smokers than in nonsmokers. To control for the maximum number of potentially confounding variables, pairs of identical twins highly discordant for cigarette smoking were selected as study subjects. Data analyses revealed 18% greater mean disc degeneration scores in the lumbar spines of smokers as compared with nonsmokers. The effect was present across the entire lumbar spine, implicating a mechanism acting systemically. This investigation demonstrates the efficiency of using carefully selected controls in studying conditions of multifactorial etiology, such as disc degeneration.     

Argon green laser treatment of peripapillary choroidal neovascular membranes

Of 27 eyes with peripapillary choroidal neovascular membranes (PPCNM), 17 (63%) had age-related macular degeneration and ten (37%) were idiopathic. PPCNM were treated in 25 eyes using the monochromatic green argon laser. Two eyes were untreatable. After an average follow-up of 37.7 months, successful closure of the choroidal new vessels was obtained in 23 eyes (92%), and visual acuity was stabilized or improved in 20 (80%). Seven eyes (28%) had recurrences; in four, the new vessels extended into the macula. Post-treatment, three eyes ultimately had dry macular scars, and one had an exudative macular scar. Of these four eyes, only the one with a dry macular scar showed visual improvement. No treated cases showed arcuate scotoma.     

Age-related macular degeneration

EPIDEMIOLOGICAL AND PATHOGENIC DATA: Age-related macular degeneration (ARMD) is the first cause of blindness in industrialized countries in patients over the age of 55. Its prevalence increases with age, affecting up to 25% of the population aged over 75. The pathogenesis of this disease is not well known. Not only aging, but also other varying degrees of genetic and environmental factors are implied. CLINICAL ASPECTS: Precursors (first clinical signs of ARMD) can be observed on examination of the fundus: drusen (localized deposits of lipids and lipoproteins) and alterations in retinal pigment epithelium (RPE) (hypo- or hyperpigmentation). Two forms of complications are observed: atrophic (or "dry") and exudative (or "wet"). The atrophic form is defined by the presence of degeneration in the central RPE, choriocapillaris and photoreceptors, resulting from the enlargement and/or coalescence of small areas of peri-foveolar atrophy (or "geographic" atrophy). The exudative form, responsible for the majority of cases of blindness due to ARMD, is characterized by the appearance of choroidal new vessels, identifiable on fluorescein angiography and responsible for serous retinal detachment, edema and hemorrhage, leading to the destruction of the macular photoreceptors. FROM A THERAPEUTIC POINT OF VIEW: Treatment of the atrophic form is currently only palliative (visual aids and re-habilitation of low vision). Treatments of the exudative form having demonstrated their efficacy are laser photocoagulation and dynamic phototherapy with verteporfine, providing relative stabilization of visual acuity in around 2/3 of the eyes. Other treatments are under evaluation: anti-angiogenic treatments, surgical techniques (ablation of the new vessels, foveal translocation), new laser treatments (transpupillary thermotherapy, selective photocoagulation of the feeder vessels). Photoreceptor and pigment epithelium transplantations or implantation of microphotodiodes represent other long-term alternatives.     

Lumbar disc degeneration: epidemiology and genetics

Research conducted over the past decade has led to a dramatic shift in the understanding of disc degeneration and its etiology. Previously, heavy physical loading-often associated with occupation-was the main suspected risk factor for disc degeneration, which was commonly viewed as a wear-and-tear phenomenon exacerbated by the precarious nutritional status of the disc. However, results of studies on twins suggest that physical loading specific to occupation and sport plays a relatively minor role in disc degeneration. Recent research indicates that heredity has a dominant role in disc degeneration, which would explain the variance of up to 74% seen in adult populations that have been studied to date. Since 1998, genetic influences have been confirmed by the identification of several gene forms associated with disc degeneration. This research is paving the way for a better understanding of the biologic mechanisms through which disc degeneration occurs, including specific interactions between genes and environment. Research into disc degeneration and genetics has become more limited by phenotypes or definitions and measures of disc degeneration than by DNA analysis. Standardized, universally accepted definitions of disc degeneration are lacking, in part due to limited knowledge of the process. The measurements that are selected depend on the method used to evaluate the disc and are often qualitative ordinal rating scales, lacking in precision. Although it is generally agreed that disc degeneration is common, the prevalence of specific findings is unclear. A review of the epidemiology of disc degeneration reveals wide-ranging prevalence estimates for various signs of disc degeneration in samples of the general population and in patients with back symptoms. The extreme variations in prevalence rates are likely largely due to inconsistencies in the definitions and measurements of disc degeneration. Such inconsistencies and inaccuracies impede epidemiologic research on disc degeneration.     

Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats

The Royal College of Surgeons (RCS) rat is an animal model for retinal degeneration such as the age-related macular degeneration. The RCS rat undergoes a progressive retinal degeneration during the early postnatal period. A potential treatment to prevent this retinal degeneration is the transplantation into the subretinal space of cells that would replace functions of the degenerating retinal pigment epithelium (RPE) cells or may form neurotrophic factors. In this study we have investigated the potential of subretinally transplanted embryonic stem cells to prevent the genetically determined photoreceptor cell degeneration in the RCS rat. Embryonic stem cells from the inner cell mass of the mouse blastocyst were allowed to differentiate to neural precursor cells in vitro and were then transplanted into the subretinal space of 20-day-old RCS rats. Transplanted and sham-operated rats were sacrificed 2 months following cell transplantation. The eyes were enucleated and photoreceptor degeneration was quantified by analyzing and determining the thickness of the outer nuclear layer by light and electron microscopy. In the eyes transplanted with embryonic cells up to 8 rows of photoreceptor cell nuclei were observed, whereas in nontreated control eyes the outer nuclear layer had degenerated completely. Transplantation of embryonic stem cells appears to delay photoreceptor cell degeneration in RCS rats.     

Tissue plasminogen activator irrigation to facilitate removal of subretinal hemorrhage during vitrectomy.

I report removing a large submacular hemorrhage by means of vitrectomy combined with use of tissue plasminogen activator (tPA) to facilitate clot removal. Four months postoperatively, the vision was 20/100 and the retina was flat, with a very thin layer of residual hemorrhage and pigmentary alteration in the macula. Although the long-term prognosis is guarded, this case does suggest that tPA may be a useful adjunct in managing selected cases of subretinal hemorrhage associated with macular degeneration.     

Complement factor H variants I890 and L1007 while commonly associated with atypical hemolytic uremic syndrome are polymorphisms with no functional significance

Mutations and polymorphisms in the gene-encoding factor H (CFH) are associated with atypical hemolytic uremic syndrome, dense deposit disease, and age-related macular degeneration. Many of these CFH genetic variations disrupt the regulatory role of factor H, supporting the concept that dysregulation of complement is a unifying pathogenic feature of these disorders. Evidence of a causal relationship with the disease is, however, not available for all CFH genetic variations found in patients, which is a potential cause of misinterpretations with important consequences for the patients and their relatives. CFH I890 and L1007 are two genetic variations repeatedly associated with atypical hemolytic uremic syndrome and also found in patients with dense deposit disease and age-related macular degeneration. Here we report an extensive genetic and functional analysis of these CFH variants. Our results indicate that I890 and L1007 segregate together as part of a distinct and relatively infrequent CFH haplotype in Caucasians. Extensive analysis of the S890/V1007 (control) and I890/L1007 (disease-associated) factor H protein variants failed to provide evidence that these amino acid changes have functional implications. Thus, the presence of the I890 and L1007 variants in healthy individuals and their high frequency in sub-Saharan African and African-American populations strongly suggest that I890 and L1007 are rare factor H polymorphisms unrelated to disease.     

Iatrogenic choroidal neovascularization after krypton red laser photocoagulation

A major cause for failure of krypton red laser photocoagulation in patients with exudative age-related macular degeneration has been the development of recurrent choroidal neovascularization adjacent to the previously treated areas. After reviewing the possible causes of recurrences, it is apparent that a certain number are iatrogenic, ie, induced by krypton red laser causing disruption and damage to the pigment epithelium-Bruch's membrane-choroidal complex. We describe three separate episodes in two patients of iatrogenic recurrent choroidal neovascularization after krypton red laser photocoagulation.     

Transplantation of autologous iris pigment epithelium to the subretinal space in rabbits.

BACKGROUND: Transplantation of autologous iris pigment epithelium (IPE) into the subretinal space has been suggested as one approach for the treatment of age-related macular degeneration. Autologous rabbit IPE cells were transplanted to the subretinal space to define the technique of transplantation and examine the survival of the transplanted cells. METHODS: Autologous IPE cells were harvested by iridectomy and transplanted directly to the subretinal space of the fellow eye in 25 rabbits, using the parsplana approach. Animals were killed over a period of 5 months, and the retinas were examined morphologically by light and electron microscopy. RESULTS: Autologous IPE cells survived and formed a polarized monolayer above the retinal pigment epithelium in the subretinal space, with apical microvilli adjacent to photoreceptors. Fragments of phagocytosed photoreceptor rod outer segments were observed in phagosomes in the cytoplasm of IPE cells. Adjacent rod outer segments remained healthy throughout the experimental period. No signs of a cell-mediated immunologic response were observed. CONCLUSIONS: Our results show that in rabbits, autologous IPE cells transplanted to the subretinal space survive and do not adversely affect the photoreceptors. These results suggest that in humans, IPE cells might provide a substitute for retinal pigment epithelium cells as autologous transplants for the treatment of age-related macular degeneration.     

Transsclerally-fixated posterior chamber intraocular implants without capsular support in penetrating keratoplasty.

The results of 36 patients who underwent penetrating keratoplasty with transscleral fixation of a posterior chamber intraocular lens are reviewed. A 13.75-millimeter "Revlens," which has the configuration of an open-loop anterior chamber lens, was used in all of the cases and gave good stability in the ciliary sulcus. The 10-0 Prolene sutures used to secure the implants were burrowed through the sclera and exited sufficiently far from the limbus to be adequately covered by Tenon's capsule and conjunctiva. No sutures eroded through the conjunctiva or needed to be removed. Two grafts became opaque, one from rejection and the other from uncontrolled glaucoma. No vitreous hemorrhage or retinal detachment occurred. Ten patients (27.8%) had cystoid macular edema diagnosed either before or after surgery; three had age-related macular degeneration; and two had traumatic macular scars. Sixteen eyes (44.4%) had final visual acuities of 20/40 or better and 25 (69.4%) saw 20/200 or better. Mean follow up was 16.8 months (range, 9 to 36 months).     

Nasopharyngeal cancer in monozygotic twins: A case report and review of the role of genetics and the environment

Introduction and importanceNasopharyngeal carcinoma (NPC) is considered a rare malignant head and neck tumour. However, the importance of genetics and environmental factors in the epidemiology of NPC is still unclear. Twins represent an excellent study population for genetic epidemiology; this is especially true of monozygotic-type twins because they are genetically identical. The difference in cancer occurrence between monozygotic twins is typically interpreted as a result of possible environmental factors.Case presentation and clinical discussionWe present the first case report of monozygotic twins with NPC. The twins' significant features are homogenous presentation, tumour location (both left-sided) and identical histology; therefore, the prognoses may be similar. Environmental factors could not be addressed in these twins because they shared the same background, and at the same time, they had no potential known contributing factors.ConclusionHaving one of the twins affected is a strong and easily recognisable risk factor for developing NPC in the other. This strong association suggests the need for regular screening of the second twin for early diagnosis of NPC.     

Monozygotic twins non-concordant for oligomeganephronic renal hypoplasia: artery-vein placental shunting as a possible pathogenetic mechanism

The etiology and pathogenesis of oligomeganephronic renal hypoplasia (OMN) are not known. In the present paper a second case of monozygotic twins non-concordant for OMN is described. It is hypothesized that one of the mechanisms which have been proposed to explain structural defects in monozygotic twins, namely placental artery-vein shunting, may have been involved in the pathogenesis of OMN in these patients. In OMN in general vascular abnormalities may have to be considered as a pathogenetic mechanism.     

Neovascular AMD: an overlooked risk factor for injurious falls

Summary   

While those with neovascular age-related macular degeneration (NV-AMD) may be at increased risk of injurious falls risk due to poor central vision and suboptimal responses when falling, preserved peripheral vision and decreased activity levels may actually be protective. Compared with control participants, patients with NV-AMD had a significantly greater number of falls and almost twice the risk of injurious falls.     

Mirror-image trigger thumb in dichorionic identical twins

The congenital vs acquired etiology of pediatric trigger thumb is the subject of considerable debate. Existing case reports of bilateral presentation in identical twins and first-degree familial association support the congenital hypothesis. However, prospective studies have yet to report a neonate presenting with this anomaly at birth. This article describes the first known set of dichorionic, monozygotic identical twins with unilateral trigger thumbs, affecting contralateral (mirror-image) hands and with asynchronous age at presentation (11 months and 18 months, respectively).Pediatric trigger thumb is caused by a mismatch between the flexor pollicis longus tendon and its A1 synovial pulley. Four sets of twins have been previously reported in the literature with trigger thumb. Of these, 3 sets were monozygotic twins who had bilaterally affected thumbs. Together with the absence of trauma, a congenital etiology was suggested. The fact that pediatric trigger thumb is generally seen several months after birth was felt to be due to infants holding their thumbs clutched in their palms until 6 months. However, no confirmed cases of trigger thumb have been diagnosed at birth in several large prospective studies of newborns.In the current case, the asynchronous presentation of unilateral trigger thumbs in identical twins does not support a solely congenital cause. Furthermore, the mirror-image presentation contradicts current embryological understanding of the temporal course of twinning and the determination of laterality. Thus, a multifactorial etiology is supported with both a genetic and acquired component affecting the development of this condition.     

Ruptured internal carotid aneurysm resulting from neurofibromatosis: treatment with intraluminal stent graft

PURPOSE: This report shows a method of treatment for life-threatening hemorrhage due to rupture of an aneurysm in the cervical internal carotid artery caused by neurofibromatosis. METHODS: Ten days after delivery of healthy twins, a 28-year-old woman with known neurofibromatosis had sudden massive swelling in the left neck. After initial tracheostomy, angiography confirmed rupture of the mid cervical internal carotid artery as well as contribution to the resultant pseudoaneurysm from external carotid branches. Treatment began with coil embolization of the external carotid branches. The internal carotid lesion, a defect approximately 1 cm in length, was then closed through use of two stent grafts, each made from Palmaz stents and 3-mm polytetrafluorethylene grafts predilated to 6 mm. The neck hematoma was then evacuated surgically. RESULTS: Completion angiography and computed tomographic scanning confirmed control of the hemorrhage. The patient survived neurologically intact with the exception of cranial nerve deficits caused by the hemorrhage. The tracheostomy tube was removed 3 weeks postoperatively. Follow-up computed tomographic scanning showed a gradual decrease in the size of the cervical soft tissue and no recurrent aneurysm. CONCLUSION: Neurofibromatosis is a rare cause of aneurysmal degeneration of blood vessels. Repair of a ruptured cervical internal carotid artery aneurysm, though feasible, is difficult with stent grafts; however, this is a better option than surgical intervention in inaccessible vessels.