July 2002: 66-year-old female with a one-year history of progressive left proptosis

The July 2002 Case of the Month (COM). This 66-year-old Caucasian female presented with gradually increasing protrusion of her left eye over a one-year period. She complained of increased tearing and foreign body sensation. The physical examination revealed a visual acuity of 20/20, normal color testing, full vision field with motility of her left eye limited in lateral gaze. Pupils were round, symmetric, with no afferent pupillary defect noted. On external examination, her left eye was grossly proptotic with resistance to retropulsion. She had 4 mm proptosis of the left eye. Computed tomography and MR imaging demonstrated a left retro-orbital mass with gadolinium enhancement and focal remodeling of orbital bones. She underwent surgical resection of tumor with a diagnosis of solitary fibrous tumor, and postoperatively she was symptom free. The histopathological differential diagnoses of spindle cell neoplasms of the orbit are discussed. Five months after surgery, no evidence of tumor recurrence was seen on neuroimaging and her vision was 20/20.     

Outcome of referrals by optometrists to general practitioners: an 18 month study in one practice.

All general ophthalmic services forms (GOS18) received by one practice over an 18 month period were analysed and the patient outcome after two years noted from the practice records. Sixty one forms were collected. Fifty patients (82%) were referred by the general practitioners to the local eye hospital. Among the 45 patients that have so far been seen by an ophthalmologist, 22 (49%) were diagnosed as having cataracts, eight (18%) macular degeneration and two (4%) glaucoma. Thirteen patients (29%) were found to have normal eyes. Nine of the 61 patients (15%) were not referred to an ophthalmologist and two patients (3%) were already under review at the eye hospital. It is concluded that some referrals to ophthalmologists might be avoided if general practitioners received improved training in ophthalmology, However, general practitioners remain an effective filter in the referral system between optometrists and ophthalmologists.     

Subtenonial application of triamcinolone in neovascular form of senile macular degeneration

The aim of this prospective study was to investigate the effectiveness of sub-tenon application of triamcinolone for neovascular age-related macular degeneration. The study included 38 eyes (26 patients; 14 women and 12 men, aged 63 to 82 years) with newly diagnosed subfoveal neovascular age-related macular degeneration. Each eye received sub-tenon injection of 0.5 mL suspension of triamcinolone-acetonide (20 mg of active substance). Follow up period was 12 months. After initial application, the injections were repeated on individual case, none to five times. Elevated intraocular pressure occurred in five patients (seven eyes) and was treated with topical antiglaucomatous therapy. Transient ptosis of upper eyelid occurred in one case and completely recovered in two days. The mean visual acuity was 0.13 +/- 0.17 on the beginning of the study and 0.22 +/- 0.22 at the end of the study. Visual acuity improved in 15/38 (39%) eyes, remained unchanged in 10/38 (26%) eyes, and worsened in 13/38 (35%) eyes. Improvement by three or more lines on Snellen optotype occurred in two cases. Comparing our results to those from other authors, sub-tenon application of triamcinolone did not prove as effective as when applied intravitreally, but is substantially less expensive and easier to perform.     

Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases

Unrelated patients with achromatopsia, macular degeneration with onset under age 50 years, cone degeneration or dysfunction, cone-rod degeneration, or macular malfunction were screened for mutations in the three genes known to be associated with achromatopsia: the GNAT2 gene encoding the alpha subunit of cone transducin and the CNGA3 and CNGB3 genes encoding the alpha and beta subunits of the cone cGMP-gated cation channel. We found no examples of patients with GNAT2 mutations. Out of 36 achromats, 12 (33%) had mutations in CNGA3 (13 different mutations including five novel mutations) and 12 (33%) had mutations in CNGB3 (six different mutations including four novel mutations). All achromats with CNG mutations had residual, presumably cone function as determined by computer-averaged 30-Hz electroretinograms (ERGs). There was considerable variability in acuity and color vision, with most patients having acuities of 20/200-20/400 and complete absence of color perception, and others having acuities of 20/25-20/40 and some color vision. Two pseudodominant achromatopsia cases were uncovered, both with CNGA3 mutations, including one family in which some compound heterozygotes with achromatopsia mutations were clinically unaffected. We found two novel CNGB3 changes in three patients with juvenile macular degeneration, a phenotype not previously associated with mutations in the cone channel subunits. These patients had subnormal acuity (20/30-20/60), normal to subnormal color vision, and normal to subnormal full-field cone ERG amplitudes. Our results indicate that some patients with channel protein mutations retain residual foveal cone function. Based on our findings, CNGB3 should be considered as a candidate gene to be evaluated in patients with forms of cone dysfunction, including macular degeneration.     

Age-related macular degeneration--contemporary possibilities of treatment

Age-related macular degeneration (AMD) is a complex multifactorial disease, that affects the central region of the retina. AMD is a leading cause of blindness among people over 50 years of age in the industrialized world. Two types of macular degeneration exist, the "dry" form and the "wet-neovascular" form. Neovascular AMD is responsible for 80-90% of cases of severe, irreversible central vision loss in patients over 65 years of age with AMD. The authors present contemporary possibilities of treatment of the patients with this disease.     

雷珠单抗治疗湿性年龄相关性黄斑变性的视力改善与黄斑形态学变化相关性分析

目的 分析雷珠单抗治疗湿性年龄相关性黄斑变性的视力改善和黄斑形态学变化之间的相关性。方法 选取2014年1月~2016年2月在西安交通大学第一附属医院行雷珠单抗治疗的湿性年龄相关性黄斑变性患者43例（1眼/例）。观察治疗前后最佳矫正视力（BCVA）、黄斑中心凹厚度（CMT）及黄斑病变面积。分析视力改善与黄斑形态学变化之间的相关性。结果 治疗3个月后,BCVA升高字母数（8.93±5.70）个,CMT下降（115.35±56.24）μm,黄斑病变面积减少（2.04±0.65）mm2。治疗3个月后,BCVA变化与CMT变化之间无相关性（r=-0.170,P＞0.05）;BCVA变化与黄斑病变面积改变之间无相关性（r=-0.101,P＞0.05）。结论 雷珠单抗治疗湿性AMD具有较好疗效,提高患者视力,改善黄斑形态学,视力改善与黄斑形态学变化之间无相关性。     

Characteristics of 681 Low Vision Patients in Korea

The purpose of our study was to evaluate the characteristics and the changes of low vision patients over ten years in Korea, and to establish useful data for planning low vision services, active care and rehabilitation. We conducted a retrospective study of 681 low vision patients who visited two low vision clinics in Seoul from 1995 to 2008. Age and sex distribution, cause of low vision, type of prescribed low vision aids, and changes of the characteristics were reviewed. In result, male were more than female. The age group between 11 and 20-yr-old (18.1%) was the largest age group. Optic atrophy (28.3%) was main causes of low vision. However, elderly low vision patients is increasing and macular degeneration is becoming a leading cause of low vision (P<0.05). One thousand five low vision aids (LVAs) were prescribed for 681 patients (1.46±0.62 aids for each patient). Near LVAs were prescribed more than distance LVAs. In most patients, the use of LVAs improved both near and distance visual function. This study is the first survey of a large number of low vision patients over a ten year period in Korea. On the base of this study, the planning of low vision services and more active rehabilitation for low vision patients, especially elderly patients, need in Korea.     

Prolonged prevention of retinal degeneration with retinylamine loaded nanoparticles

Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amines, including retinylamine, are effective in lowing the concentration of all-trans-retinal within the retina and thus prevent retina degeneration in mouse models of human retinopathies. Here we achieved prolonged prevention of retinal degeneration by controlled delivery of retinylamine to the eye from polylactic acid nanoparticles in Abca4^−/−Rdh8^−/− (DKO) mice, an animal model of Stargardt disease/age-related macular degeneration. Subcutaneous administration of the nanoparticles containing retinylamine provided a constant supply of the drug to the eye for about a week and resulted in effective prolonged prevention of light-induced retinal degeneration in DKO mice. Retinylamine nanoparticles hold promise for prolonged prophylactic treatment of human retinal degenerative diseases, including Stargardt disease and age-related macular degeneration.     

Artificial vision through neuronal stimulation

Introduction

The term visual prosthesis refers to any device capable of eliciting visual percepts in an individual through electrical stimulation of any part of the visual system.

Background

Blindness can be due to eye pathology or due to damage of the lateral geniculate or visual cortex. Eye pathology other than diseases that affect the cornea and lens are numerous and some of the leading causes are diabetic retinopathy, age-related macular degeneration, retinal detachment, glaucoma, and retinal vascular occlusions.The visual prosthesis can be divided into non-retinal and retinal approaches. Non-retinal approaches include cortical and optic nerve prosthesis. Retinal approaches are aimed at eye pathologies in which at least part of the optic nerve remains intact whereas when the optic nerve is nearly completely damaged and/or the eye itself is disfigured or degenerated then a non-retinal approach is warranted. The retinal prosthesis can be placed on the surface of the retina, in the subretinal space or in the suprachoroidal space.

Results

Several independent groups related variable degrees of success in promoting visual sensations through electrical stimulation of the visual system.Every technique, equipment and anatomical target has its advantages and disadvantages, and the biological/electrical–mechanical interface is still the aspect of the research towards a chronic, long term, reliable biomimetic implant.

Conclusions

The visual prostheses have achieved significant developments in recent years. We see continued improvement in visual acuity with increasing number and density of electrodes. Even though the visual acuity is still poor relative to normal vision, these subjects can read letters using their implants. Perhaps more importantly, blind patients can use these devices for mobility and orientation.     

Review of the publications of the Nigeria national blindness survey: methodology, prevalence, causes of blindness and visual impairment and outcome of cataract surgery

This is a review of the major publications from the Nigeria national blindness survey in order to highlight major findings and challenges of eye care in Nigeria. The review summarizes methodology and key findings. Survey publications on methodology, prevalence and causes of visual impairment and outcome of cataract surgery were retrieved, reviewed and relevant data extracted, reported and discussed. The study was the largest and more detailed eye survey in Nigeria (15,375 people 40 years and older recruited). Participants had detailed eye examination including visual acuity, autorefractokeratometry, A- scan biometry, visual field and basic eye examination. Cause(s) of visual impairment in each eye using WHO algorithm was determined among participants with vision < 6/12. Some of the participants also had qualitative questions on barriers to uptake of services, quality of life and visual function. Major highlights of the results as contained in the publications include a high prevalence of blindness with 4.2% (95% CI: 3.8-4.6%;),of the study population having blindness (using presenting vision (PVA)) even with best correction the prevalence was 3.4% (95% CI: 3.0-3.8%. The prevalence of SVI using PVA was 1.5% (95% CI: 1.3-1.7%).and with best correction 0.8% (95% CI: 0.7-1.0%). Blindness varied by age groups, sex, literacy level and geopolitical zone. Furthermore, 84% of blindness was due to avoidable causes with cataract responsible for 43% of blindness, glaucoma 16.7%, uncorrected aphakia 8.4% and corneal opacity 7.9%. Of the total 538 eyes that had cataract surgery procedures, 42.7% had couching and the remaining had cataract surgery, but only 41.4% of cataract operated eyes had IOL surgery. Outcome of cataract surgery was good at presentation for only 30.8% of eyes (84 eyes) which improved to 56.8% with correction. The possible remedy for the high burden of needless blindness and harmful eye health practices in Nigeria are discussed.     

Short-Term Outcomes of the First in Vivo Gene Therapy for RPE65-Mediated Retinitis Pigmentosa

Here, we report early treatment outcomes of gene therapy for early onset retinitis pigmentosa (RP) (Leber congenital amaurosis) associated with biallelic RPE65 mutation in a 30-year-old female patient. Initially, her visual acuity (VA) was 20/200, and her visual field (VF) was severely constricted to the center in the left eye. Her electroretinography showed nearly extinct signals. Full-field stimulus threshold test (FST) revealed diminished dark-adapted light sensitivity. Voretigene neparvovec-rzyl (VN) is the first in vivo viral gene therapy agent to be approved. At 3 months after subretinal injection of VN in the left eye, VA, VF, and FST showed sustained improvement. She did not exhibit any signs of adverse effects from the treatment. Gene therapy for RP proved to be an effective and safe treatment in an advanced case of RPE65-associatied early onset RP.     

Effect of tongue stimulation on nystagmus eye movements in blind patients

We have observed dramatic effects of tactile tongue stimulation on nystagmus eye movements in patients with acquired blindness, and we report these results. Six adult subjects (3 subjects with light perception or worse vision and 3 normal subjects) were included in this study. Causes of blindness included traumatic explosion, anterior ischemic optic neuropathy, and central retinal artery occlusion. Duration of blindness was 15, 3 and 1.5 years, respectively. A video eye tracking system (Eyelink 1000) was used to record eye movements. The eye movement recording (EMR) was repeated four times in a span of 20 min. Two of the EMRs were performed without tongue stimulation and two with tongue stimulation in randomized order. A tongue stimulus was applied to the surface of the tongue using a Brainport device that produces an electrical tactile stimulus. The nystagmus waveform characteristics and frequency were analyzed. We found that all blind subjects showed continuous jerk nystagmus with slow and quick phases, mainly in horizontal plane in their primary eye positions. The recorded nystagmus waveforms were jerk with linear velocity slow phases. When the tongue stimulus was applied, the frequency of nystagmus was significantly reduced by 47, 40, and 11%, and relative amplitude was reduced by 43, 45, and 6% for three blind subjects, respectively. In conclusion, we think our results that tongue stimulation influences nystagmus eye movements support a link between non-visual sensory input and ocular motor activity.     

A retrospective review of visual outcome and complications in the treatment of retinoblastoma

The aim of this study was to look at the visual outcome and treatment complications of children diagnosed with Retinoblastoma during the years 1985-2003 inclusive. A retrospective review of all patients records was performed. Patient characteristics, treatment methods and complications were recorded. Twenty eight children presented to Temple street Hospital between 1985-2003. Six of these infants had bilateral tumours. The mean age at presentation was 23.7 months. Sixty-nine percent presented with Leucocoria, of these 33% also had a squint. The mean duration of symptoms was only known in 58% and this figure was approximately 19.8 months. Enucleation was performed in 24 eyes of 24 patients. Three patients required adjuvant chemotherapy post enucleation. Two eyes was treated with external beam radiation and one eye with plaque radiotherapy. One eye (second eye) was treated with systemic chemotherapy and radiation. Five eyes of three patients were treated with systemic chemotherapy followed by adjuvant Argon laser, cryotherapy and diode laser to each eye.The complications of each treatment group was recorded. The visual outcome in the salvaged eyes was favourable. There were no deaths recorded. Though chemotherapy with adjuvant local treatments provide adequate treatment for early tumours, enucleation still plays a major role in the treatment of Retinoblastoma. The total eye salvage rate in this study was 29% with an enucleation rate of 90% in unilateral cases and 33% in bilateral cases. Sixty-six percent of bilateral eyes affected were salvaged. Seventy-one percent of tumours were diagnosed after a parent noticed a gross abnormality of the eye. This highlights the possible need for screening for retinoblastoma in the infant population.     

Three-year clinical and optical coherence tomography follow-up after stereotactic radiotherapy for neovascular age-related macular degeneration

PurposeThe long-term clinical outcome of adjuvant stereotactic radiotherapy (SRT) in neovascular age-related macular degeneration (nAMD) patients was evaluated.MethodsThis case-control study included patients with unilateral nAMD, who underwent SRT complementary to standard anti-VEGF treatment. Only patients with monthly follow-up over at least three years were considered. Number of intravitreal injections, visual acuity (VA), central retinal thickness (CRT), and subfoveal choroidal thickness (SFCT) were evaluated and compared to baseline as well as to an age- and gender-matched control group, who received anti-VEGF monotherapy.ResultsTwenty patients were irradiated and had complete follow-up. Cumulatively, SRT patients needed significantly less injections than non-irradiated ones over three years (14 vs. 18, p ​= ​0.014), while median VA did not show statistically significant changes (0.4 logMAR at baseline to 0.65 logMAR at final follow-up, p ​= ​0.061). CRT remained steady, but SFCT showed a continuous thinning of almost 50 ​μm (p ​= ​0.031) in irradiated patients over three years. Multiple linear regression analysis revealed that SFCT and VA at time of irradiation are significant prognostic factors of VA change in SRT patients over the following three years (F(2,17) ​= ​23.946, p<0.001, R² of 0.738).ConclusionsSRT significantly reduced the cumulative anti-VEGF treatment burden over three years, however, this was mainly driven by the results of the first year after irradiation. A thinner SFCT at time of irradiation was associated with poorer visual outcome. While further research and investigation are warranted to elucidate the underlying pathogenesis, SFCT could be a potential biomarker when evaluating a patient’s suitability for SRT.     

Central serous chorioretinopathy in African Americans

PURPOSE: Central Serous Chorioretinopathy (CSCR) is presumed to be less prevalent in the African American population. The purpose of this study was to compare the characteristics of CSCR in African Americans and Caucasians. METHODS: A retrospective analysis was performed. Visual acuity (VA) evaluations that were recorded included best-corrected VA at diagnosis, worst VA recorded at follow-up, and best-corrected VA at the last clinic visit. Recurrences of CSCR, frequency of laser photocoagulation, and fluorescein angiographic patterns also were evaluated. RESULTS: Of the 74 patients with CSCR, 15 (20.3%) were African American and 59 (79.7%) were Caucasian. This ethnic distribution was similar to the ethnic distribution in the entire Henry Ford Health System population. The mean VA at presentation was significantly lower in African-Americans (20/55 vs. 20/30, P=0.004) and trended towards being lower during follow-up (20/58 vs. 20/32, P=0.04) and at final examination (20/28 vs. 20/22, P=0.04). Mean length of follow-up was 21 months for both groups. CONCLUSION: The rates and spectrum of symptomatic CSCR seen at Henry Ford Health System are comparable in African Americans and Caucasians.     

Twenty year review of histopathological findings in enucleated/eviscerated eyes

BACKGROUND/AIMS: To evaluate the need for routine histopathological analysis of enucleated/eviscerated eyes and changes in indications for eye removal. METHODS: Retrospective review of all enucleation/evisceration histopathology reports over 20 years. Clinical history was correlated with pathological findings. Two 10 year periods (1984-93, 1994-2003) were compared to detect changes in indications for eye removal. RESULTS: In total, 285 histopathology results were traced from 1984 to 2003; 161 and 124 were evisceration and enucleation specimens, respectively. Glaucoma, malignant melanoma, trauma, and retinal detachment were the most frequent diagnoses 1984-1993. Ocular trauma was the most frequent diagnosis 1994-2003, followed by phthisis bulbi and endophthalmitis. Three cases were diagnosed as metastatic carcinoma; all were suspected preoperatively. A fourth case was a diagnostic surprise: adenocarcinoma found in an eye removed for pain and phthisis. Comparison of two 10 year periods showed a decrease in the number of enucleations/eviscerations, perhaps reflecting a decrease in the number of specimens sent. A preference for eviscerations was evident over the 20 years. CONCLUSION: The number of eyes removed and histologically analysed decreased in the period 1994 to 2003, perhaps because of better treatment options, allowing globe preservation. There was a significant shift in the diagnosis in the two time periods, and a preference for evisceration in both. Only one diagnostic surprise was discovered (0.35%). This study does not support the need to send all globes/contents for histopathological examination. However, because of the one unexpected finding, it is recommended where the examination is incomplete or the history of visual loss is unclear.     

The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration.     

Lexical patterns, features and knowledge resources for coreference resolution in clinical notes

Generation of entity coreference chains provides a means to extract linked narrative events from clinical notes, but despite being a well-researched topic in natural language processing, general-purpose coreference tools perform poorly on clinical texts. This paper presents a knowledge-centric and pattern-based approach to resolving coreference across a wide variety of clinical records from two corpora (Ontology Development and Information Extraction (ODIE) and i2b2/VA), and describes a method for generating coreference chains using progressively pruned linked lists that reduces the search space and facilitates evaluation by a number of metrics. Independent evaluation results give an F-measure for each corpus of 79.2% and 87.5%, respectively. A baseline of blind coreference of mentions of the same class gives F-measures of 65.3% and 51.9% respectively. For the ODIE corpus, recall is significantly improved over the baseline (p<0.05) but overall there was no statistically significant improvement in F-measure (p>0.05). For the i2b2/VA corpus, recall, precision, and F-measure are significantly improved over the baseline (p<0.05). Overall, our approach offers performance at least as good as human annotators and greatly increased performance over general-purpose tools. The system uses a number of open-source components that are available to download.     

Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive disorder characterized by diabetes mellitus (DM), progressive sensorineural deafness, and thiamine-responsive anemia. Mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter protein THTR-1 are responsible for the clinical features associated with TRMA syndrome. We report an African-American female with TRMA-syndrome associated with thyroid disease and retinitis pigmentosa caused by a novel mutation in the SLC19A2 gene. The patient presented at 12 months of age with paroxysmal atrial tachycardia and hepatosplenomegaly. One month later, she developed DM requiring intermittent insulin therapy. At 2-1/2 years of age, profound sensorineural hearing loss was discovered. By 4 years of age, daily insulin therapy (0.5 U/kg/day) was instituted and her insulin requirement gradually increased to 1.0 U/kg/day by 9 years of age. She developed optic atrophy, retinitis pigmentosa, and visual impairment by 12 years of age with severe restriction of peripheral vision by 16 years. At age 19, a thiamine-responsive normocytic anemia was discovered. She was diagnosed with autoimmune thyroiditis at 20 years and she experienced a psychotic episode associated with a mood disorder at age 21. With oral thiamine therapy, her insulin requirement decreased by 30% over a 20 month period. Molecular analysis revealed that the patient is homozygous for a missense mutation (C152T) in exon 1 of the SLC19A2 gene.