Ocular Involvement in Hereditary Amyloidosis.

The term amyloidosis describes a group of rare diseases caused by protein conformation abnormalities resulting in extracellular deposition and accumulation of insoluble fibrillar aggregates. So far, 36 amyloid precursor proteins have been identified, and each one is responsible for a specific disease entity. Transthyretin amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, due to the deposition of transthyretin (TTR), which is a transport protein mainly synthesized in the liver but also in the retinal pigment epithelial cells. ATTRv amyloidosis may be misdiagnosed with several other conditions, resulting in a significant diagnostic delay. Gelsolin and keratoepithelin are other proteins that, when mutated, are responsible for a systemic amyloid disease with significant ocular manifestations that not infrequently appear before systemic involvement. The main signs of ocular amyloid deposition are in the cornea, irido-corneal angle and vitreous, causing complications related to vasculopathy and neuropathy at the local level. This review aims at describing the main biochemical, histopathological and clinical features of systemic amyloidosis associated with eye involvement, with particular emphasis on the inherited forms. We discuss currently available treatments, focusing on ocular involvement and specific ophthalmologic management and highlighting the importance of a prompt treatment for the potential sight-threatening complications derived from amyloid deposition in ocular tissues.

New Highlights of Resveratrol: A Review of Properties against Ocular Diseases.

Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV's potential adjuvant activity.

Validity of International Classification of Diseases Codes for Identifying Neuro-Ophthalmic Disease in Large Data Sets: A Systematic Review.

BACKGROUND: Administrative health claims data have been used for research in neuro-ophthalmology, but the validity of International Classification of Diseases (ICD) codes for identifying neuro-ophthalmic conditions is unclear. EVIDENCE ACQUISITION: We performed a systematic literature review to assess the validity of administrative claims data for identifying patients with neuro-ophthalmic disorders. Two reviewers independently reviewed all eligible full-length articles and used a standardized abstraction form to identify ICD code-based definitions for 9 neuro-ophthalmic conditions and their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A quality assessment of eligible studies was also performed. RESULTS: Eleven articles that met criteria for inclusion are as follows: 3 studies of idiopathic intracranial hypertension (PPV 54%-91% and NPV 74%-85%), 2 studies of giant cell arteritis (sensitivity 30%-96% and PPV 94%), 3 studies of optic neuritis (sensitivity 76%-99%, specificity 83%-100%, PPV 25%-100%, and NPV 98%-100%), 1 study of neuromyelitis optica (sensitivity 60%, specificity 100%, PPV 43%-100%, and NPV 98%-100%), 1 study of ocular motor cranial neuropathies (PPV 98%-99%), and 2 studies of myasthenia gravis (sensitivity 53%-97%, specificity 99%-100%, PPV 5%-90%, and NPV 100%). No studies met eligibility criteria for nonarteritic ischemic optic neuropathy, thyroid eye disease, and blepharospasm. Approximately 45.5% provided only one measure of diagnostic accuracy. Complete information about the validation cohorts, inclusion/exclusion criteria, data collection methods, and expertise of those reviewing charts for diagnostic accuracy was missing in 90.9%, 72.7%, 81.8%, and 36.4% of studies, respectively. CONCLUSIONS: Few studies have reported the validity of ICD codes for neuro-ophthalmic conditions. The range of diagnostic accuracy for some disorders and study quality varied widely. This should be taken into consideration when interpreting studies of neuro-ophthalmic conditions using administrative claims data.

Triaging ophthalmology outpatient referrals with machine learning: A pilot study.

IMPORTANCE: Triaging of outpatient referrals to ophthalmology services is required for the maintenance of patient care and appropriate resource allocation. Machine learning (ML), in particular natural language processing, may be able to assist with the triaging process. BACKGROUND: To determine whether ML can accurately predict triage category based on ophthalmology outpatient referrals. DESIGN: Retrospective cohort study. PARTICIPANTS: The data of 208 participants was included in the project. METHODS: The synopses of consecutive ophthalmology outpatient referrals at a tertiary hospital were extracted along with their triage categorizations. Following pre-processing, ML models were applied to determine how accurately they could predict the likely triage categorization allocated. Data was split into training and testing sets (75%/25% split). ML models were tested on an unseen test set, after development on the training dataset. MAIN OUTCOME MEASURE: Area under the receiver operator curve (AUC) for category one vs non-category one classification. RESULTS: For the main outcome measure, convolutional neural network (CNN) provided the best AUC (0.83) and accuracy on the test set (0.81), with the artificial neural network (AUC 0.81 and accuracy 0.77) being the next best performing model. When the CNN was applied to the classification task of identifying which referrals should be allocated a category one vs category two vs category three priority, a lower accuracy was achieved (0.65). CONCLUSIONS AND RELEVANCE: ML may be able to accurately assist with the triaging of ophthalmology referrals. Future studies with data from multiple centres and larger sample sizes may be beneficial.

Long non-coding RNAs in ocular diseases: new and potential therapeutic targets.

Long non-coding RNAs (lncRNAs) are non-protein coding transcripts containing more than 200 nucleotides. In the past, lncRNAs were considered as 'transcript noise' or 'pseudogenes' and were thus ignored. However, in recent years, lncRNAs have been proven to regulate gene expression at the epigenetic, transcriptional and translational level, and thereby influence cell proliferation, apoptosis, viability, immune response and oxidative stress. Furthermore, increasing evidence points to their involvement in different diseases, including cancer and heart diseases. Recently, lncRNAs were shown to be differentially expressed in ocular tissues and play a significant role in the pathogenesis of ophthalmological disorders such as glaucoma, corneal diseases, cataract, diabetic retinopathy, proliferative vitreoretinopathy and ocular tumors. In this review, we summarize the classification and mechanisms of known lncRNAs, while detailing their biological functions and roles in ocular diseases. Moreover, we provide a concise review of the clinical relevance of lncRNAs as novel, potential therapeutic targets in the treatment of eye diseases.

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder.

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme's metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher's can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 - present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

Clinical Registries in Ophthalmology.

TOPIC: Clinical registries in ophthalmology. CLINICAL RELEVANCE: In recent years, advancements in digital technology and increasing use of electronic medical records in health systems have led to the dramatic growth in large clinical data sets. Clinical data registries are organized systems that collect data on patients diagnosed with a disease or condition or who undergo a certain procedure. METHODS: A search of the PUBMED database was conducted in January 2018 for clinical registries in ophthalmology. RESULTS: Ninety-seven clinical eye registries were found, with significant growth in numbers in the last 4 decades. The most common conditions captured were blindness or low vision, corneal transplantation, glaucoma, and cataract surgery. Most registries originate in the European region, North America, and Australia. Nine registries had multinational coverage, whereas 48 were national registries. As the numbers and scope of clinical registries have expanded, valuable observational data have been used to study real-world clinical outcomes in healthcare quality measurement and improvement and to develop new guidelines and standards. Pertinent areas of its use include studying treatments and outcomes in cataract surgery, corneal transplantation, and macular degeneration. CONCLUSIONS: The use of clinical registries for quality improvement and research has grown significantly in the last few decades, and this trend will continue as information technology infrastructures develop.

Frequency of ocular diseases among recipients of disability benefits in the metropolitan region of Recife, Brazil / Incapacidade para o trabalho por doenças oculares na população segurada da Previdência Social da região metropolitana do Recife, Brasil: um estudo de frequência

ABSTRACT Purpose: To identify the frequency of ocular diseases among recipients of disability benefits in the metropolitan region of Recife, Brazil. Methods: A review was performed of 217,221 cases of disability benefits granted between 2010 and 2015 by the executive managerial department of the Brazilian National Institute of Social Security (Instituto Nacional do Seguro Social [INSS]) in Recife, which encompasses 14 municipalities of the metropolitan region, including the capital. The frequencies of the identified cases of ocular morbidity were then determined according to their group in the International Classification of Diseases, 10th Revision (ICD-10), their cause, the age, sex, and income of the recipient, and the type and duration of the benefit. Results: Of all disability benefits granted, 5,324 (2.5%) were due to ocular disease, the majority (91.1%) consisting of sick pay. Most of the beneficiaries (64.6%) were males, were 20 to 59 years of age, and 61.2% earned the minimum wage or less. The principal ocular diseases for which sick pay benefits were granted were cataract (24.5%), conjunctivitis (21.1%), and pterygium (8.8%). Blindness and low vision were the principal ocular diseases in cases of accident indemnity and disability retirement. Conclusions: The results highlight the magnitude of the problem of ocular diseases to the social security system, with serious economic and social losses, and emphasize the need for measures aimed at their prevention. Moreover, integration between the national departments of health and social security needs to be improved.

RESUMO Objetivo: Identificar a frequência das doenças oculares entre os segurados com benefícios por incapacidade. Métodos: Estudo retrospectivo de 217.221 benefícios por incapacidade concedidos pelo Instituto Nacional do Seguro Social (INSS) da gerência executiva de Recife, que engloba os 14 municípios da região metropolitana, incluindo a capital, no período de 2010-2015. Os casos de doenças oculares foram avaliados quanto à frequência considerando seu grupo na CID-10. Foi feita ainda uma análise do perfil dos benefícios concedidos por estas doenças com relação à causa, idade, sexo, faixa salarial, espécie e duração do benefício. Resultados Do total dos benefícios concedidos, 5.324 foram decorrentes de doenças oftalmológicas (2,5%) e entre estes, a maioria como auxíliodoença (91,1%). Houve predomínio do sexo masculino (64,6%), faixa etária dos 20 aos 59 anos e valor de até 01 salário mínimo (61,2%). Entre as concessões de auxíliodoença a principal causa foi a catarata (24,5%), seguida pela conjuntivite (21,1%) e pterígio (8,8%). A cegueira e baixa visão foi a principal causa de auxílio-acidente e aposentadoria por invalidez. Conclusões: Os resultados destacam a magnitude do problema das doenças oculares para a Previdência Social, com graves perdas econômicas e sociais, e enfatizam a necessidade de medidas que visem sua prevenção e maior integração entre os serviços de saúde e o INSS (Instituto Nacional do Seguro Social).

Peripapillary choroidal thickness in contralateral eyes after evisceration of diseased eyes / Espessura coroide peripapilar de olhos contralaterais após evisceração do olho doente

ABSTRACT Purpose: To evaluate peripapillary choroidal thickness changes in contralateral eyes of patients who had undergone evisceration of their diseased eyes. Methods: In this retrospective study, peripapillary choroidal thickness parameters in 34 eyes of 34 patients who had undergone diseased-eye evisceration between March 2014 and May 2016 were evaluated using spectral domain optical coherence tomography. The scans were manually delineated to identify the principal surfaces of Bruch's membrane, the Bruch's membrane opening, and the anterior sclera. Peripapillary choroidal thickness was measured between the Bruch's membrane and the anterior sclera at increasing distance away from the Bruch's membrane opening. The mean peripapillary choroidal thickness values in the contralateral eyes of the patients and those of the control group were compared. Results: The mean peripapillary choroidal thickness was higher in the contralateral eyes of the patients compared with that of normal eyes at all distances from the Bruch's membrane opening. Conclusion: Increased peripapillary choroidal thickness was noted in the contralateral eyes of the patients, potentially resulting in a thicker choroid. Although further investigation is required to determine the cause, these findings indicate the presence of a compensatory factor in the contralateral eyes.

RESUMO Objetivo: Avaliar as alterações da espessura coroide peripapilar em olhos contralaterais de pacientes submetidos à evisceração do olho doente. Métodos: Neste estudo retrospectivo, parâmetros da espessura coróide peripapilar de 34 olhos de 34 pacientes submetidos à evisceração, entre março de 2014 e maio de 2016, foram avaliados com tomografia de coerência óptica de domínio espectral. As varreduras foram manualmente delineadas para identificar as principais superfícies da membrana de Bruch, a abertura da membrana de Bruch e a esclera anterior. A espessura coroide peripapilar foi medida entre a membrana de Bruch e a esclera anterior a uma distância crescente da abertura da membrana de Bruch. Compararam-se os valores médios da espessura coroide peripapilar dos olhos contralaterais dos pacientes e do grupo controle. Resultados: A espessura coroide peripapilar média foi mais espessa nos olhos contralaterais dos pacientes, quando comparada com os olhos normais, em todas as distâncias da abertura da membrana de Bruch. Conclusão: O aumento da espessura coroide peripapilar foi notado nos olhos contralaterais dos pacientes. O espessamento da coroide pode ser resultante do distúrbio. Embora seja necessária uma investigação mais aprofundada para determinar a causalidade, esses achados podem apontar para um fator compensatório dos olhos contralaterais.

The Classification and Prognosis of Periocular Complications Related to Blindness following Cosmetic Filler Injection.

Common side effects during hyaluronic acid filler injections are typically mild and reversible, but several reports of blindness have received attention. The present study focused on orbital symptoms combined with blindness, aiming to classify affected patients and predict their disease course and prognosis. From September of 2012 to August of 2015, nine patients with vision loss after filler injection were retrospectively reviewed. Ptosis, ophthalmoplegia, and enophthalmos were recorded over a 6-month follow-up, and patients were classified into four types according to periocular symptom manifestation. Two patients were categorized as type I (blindness without ptosis or ophthalmoplegia), two patients as type II (blindness and ptosis without ophthalmoplegia), two patients as type III (blindness and ophthalmoplegia without ptosis), and three patients as type IV (blindness with ptosis and ophthalmoplegia). The present study includes previously unpublished information about orbital symptom manifestations and prognosis combined with blindness caused by retinal artery occlusion after cosmetic filler injection. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Manual Removal of Intraocular Lens Silicone Oil Droplets and Dystrophic Calcifications Using a Nitinol Loop: A Case Series.

Deposition of dystrophic calcifications on the posterior surface of silicone intraocular lenses (IOLs) has been reported in patients with asteroid hyalosis. Accumulation of silicone oil droplets on the posterior surface of silicone IOLs in silicone-filled eyes has also been reported. Recently, a novel technique to manually remove dystrophic calcifications using a nickel titanium loop (Finesse Flex Loop; Alcon, Fort Worth, TX) was described, obviating the need for IOL exchange. Here, the authors report their outcomes with this technique in five eyes with IOL dystrophic calcifications as well as one eye with IOL silicone oil droplet accumulation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:422-426.].

Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

Ocular pyoderma gangrenosum: A systematic review.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare, ulcerative cutaneous disorder. Ophthalmic involvement in PG is atypical, but can have devastating consequences. OBJECTIVE: We sought to characterize ocular PG to allow for earlier diagnosis and therapy. To our knowledge, this is the first systematic review summarizing this clinical variant. METHODS: A systematic review was conducted using PubMed and Web of Science. Data were extracted and studies were qualitatively assessed and analyzed. RESULTS: We identified all 34 cases of PG involving the eye and periorbital area, and categorized them into 4 different subtypes. Common presenting signs include ulceration, peripheral ulcerative keratitis, and decreased visual acuity. Although it is often difficult to biopsy ocular PG, histologic features are nonspecific. Combined therapy using corticosteroids and further surgical reconstruction as needed is the mainstay of treatment. Cases of the eye/orbit in particular should be treated aggressively, as these are more likely to relapse compared with cases of the periorbital area. LIMITATIONS: Use of case reports, paucity of ocular PG cases, and heterogeneity of studies are limitations. CONCLUSION: PG should be considered in the differential diagnosis of ulceration of ocular/periocular tissues. An aggressive, early, multimodal treatment strategy should be used to prevent relapse, especially in cases of the eye/orbit.

Evaluation of Objective Vitritis Grading Method Using Optical Coherence Tomography: Influence of Phakic Status and Previous Vitrectomy.

PURPOSE: To evaluate a proposed method for objective measurement of vitreous inflammation using a spectral-domain optical coherence tomography (SD OCT) device in a large cohort of uveitis eyes, including pseudophakic eyes and vitrectomized eyes. DESIGN: Retrospective, observational cohort study. METHODS: One hundred five uveitis eyes (105 patients) with different vitreous haze score grades according to standardized protocols and corresponding SD OCT images (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, California, USA) were included. Clinical data recorded included phakic status, previous vitreoretinal surgery, and anterior chamber (AC) cells and flare. SD OCT images were analyzed using custom software that provided absolute measurements of vitreous (VIT) and retinal pigment epithelium (RPE) signal intensities, which were compared to generate a relative optical density ratio with arbitrary units (VIT/RPE-relative intensity) and compared to VHS. RESULTS: VIT/RPE-relative intensity showed a significant positive correlation with vitreous haze score (r = 0.535, P < .001) that remained significant after adjusting for factors governing media clarity, such as AC cells, AC flare, and phakic status (R(2)-adjusted = 0.424, P < .001). Significant differences were also observed between the different vitreous haze score groups (P < .001). Preliminary observation did not observe differences in VIT/RPE-relative intensity values between phakic and pseudophakic eyes (0.3522 vs 0.3577, P = .48) and between nonvitrectomized and vitrectomized eyes (0.3540 vs 0.3580, P = .52), overall and respectively for each vitreous haze score subgroup. CONCLUSIONS: VIT/RPE-relative intensity values provide objective measurements of vitreous inflammation employing an SD OCT device. Phakic status and previous vitrectomy surgery do not appear to influence these values, although these preliminary findings need validation in future studies.

Ophthalmic diseases and disorders in free-ranging rhesus macaque (Macaca mulatta) of Shivalik hill area of Himachal Pradesh, Northern India.

BACKGROUND: The studies on ophthalmic diseases and disorders in a population of rhesus macaques, in particular with free-ranging macaques, are limited mainly by the difficulty in capturing animals and obtaining samples. METHODS: From October 2011 to 2013, prevalence of various ophthalmic affections was recorded and analyzed on the basis of sex, age-group, and disease condition both in urban and peri-urban free-ranging rhesus macaques (Macaca mulatta) from various locations in Shivalik hill areas of Himachal Pradesh in northern India, as a part of clinical health examination. RESULTS AND CONCLUSION: Ophthalmic diseases were more prevalent in macaques captured from urban settings than those from peri-urban, and difference between two groups was statistically significant (P < 0.01). Further classification of ophthalmic diseases revealed that traumatic injuries, corneal opacity, and cataract were significantly higher in urban than those in peri-urban macaque (P < 0.01). Similarly, the ophthalmic disorders among different age-groups were also found statistically significant (P < 0.01). The effect of sex on ophthalmic disorders was not found significant. Overviewing these results, disturbances in environment, close proximity to humans, and increasing age may lead to ophthalmic occurrences in these free-range macaques.

Vitreomacular traction syndrome: postoperative functional and anatomic outcomes.

BACKGROUND AND OBJECTIVE: To analyze a variety of vitreomacular traction (VMT) morphologies to establish a major classification that better reflects the preoperative predictive factors of postoperative visual and anatomic outcomes. PATIENTS AND METHODS: Thirty-six eyes submitted to vitrectomy surgery were categorized with a VMT pattern (V- or J-shaped) and diameter (focal < 1,500 µm or broad > 1,500 µm) based on optical coherence tomography. RESULTS: The researchers compared different classifications of VMT. Despite similar postoperative best corrected visual acuity (BCVA) values (P = .393), cases with focal VMT had greater visual improvement (P = .027) because the preoperative BCVA was significantly lower in the focal group (P = .007). However, the BCVA improvements did not differ between the groups regarding the classic VMT morphologic patterns (P = .235). CONCLUSION: Postoperative outcomes and macular disorders are closely related to VMT size. The adhesion diameter (focal or broad VMT) and not the classic VMT morphologic pattern (V- or J-shaped) may better predict the postoperative anatomic and functional outcomes.

Spectrum of morphological and visual changes due to vitreomacular interface disorders encountered in a large consecutive cohort of patients.

AIM: Identify the incidence of vitreomacular traction (VMT) and frequency of reduced vision in the absence of other coexisting macular pathology using a pragmatic classification system for VMT in a population of patients referred to the hospital eye service. METHODS: A detailed survey of consecutive optical coherence tomography (OCT) scans was done in a high-throughput ocular imaging service to ascertain cases of vitreomacular adhesion (VMA) and VMT using a departmental classification system. Analysis was done on the stages of traction, visual acuity, and association with other macular conditions. RESULTS: In total, 4384 OCT scan episodes of 2223 patients were performed. Two hundred and fourteen eyes had VMA/VMT, with 112 eyes having coexisting macular pathology. Of 102 patients without coexisting pathology, 57 patients had VMT grade between 2 and 8, with a negative correlation between VMT grade and number of Snellen lines (r=-0.61717). There was a distinct cutoff in visual function when VMT grade was higher than 4 with the presence of cysts and sub retinal separation and breaks in the retinal layers. CONCLUSIONS: VMT is a common encounter often associated with other coexisting macular pathology. We estimated an incidence rate of 0.01% of VMT cases with reduced vision and without coexisting macular pathology that may potentially benefit from intervention. Grading of VMT to select eyes with cyst formation as well as hole formation may be useful for targeting patients who are at higher risk of visual loss from VMT.