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ABSTRACT: To investigate the utility of corneal biopsy in the evaluation of infectious keratitis; to compare results of culture and histopathologic examination of the same specimens; to investigate potential factors related to positive biopsy results.
Retrospective, observational case series.
We reviewed medical records for all patients who underwent corneal biopsy because of infectious keratitis at the Jules Stein Eye Institute from June 1989 through June 2009. In general, biopsy specimens were both cultured and examined histopathologically. Lesion size, lesion progression, and interval from presentation to biopsy were analyzed as possible predictors of positive biopsies.
Organisms were identified in 20 of 48 (42%) consecutive biopsies (positive cultures in 9 of 47 cases [19%]; positive histopathologic examination in 19 of 47 cases [40%]). Culture and histopathologic results were concordant in 30 of 46 biopsies (65%) for which both techniques were performed; 10 of the 16 discordant cases were culture-negative/histopathology-positive, while the remaining 6 had positive but discordant results for the 2 techniques (cultures all showed bacteria; histopathologic examination showed fungi or cysts consistent with Acanthamoeba sp.). Corneal biopsy revealed microorganisms in 12 of 27 patients (44%) with negative cultures of corneal scrapings obtained at presentation. None of the potential risk factors was statistically associated with positive biopsies.
Corneal biopsy can be useful for identifying the cause of infectious keratitis in selected cases. Culture and histopathologic examination can provide complementary information, but discordant results may occur. Acanthamoebic and fungal infections are more likely to be identified by histopathologic examination.
American journal of ophthalmology 05/2012; 154(3):512-519.e2. · 3.83 Impact Factor
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ABSTRACT: To evaluate relationships between retinal vessel caliber, AIDS-related factors, and mortality.
Longitudinal, observational cohort study.
We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Semi-automated evaluation of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, identified independent relationships between indices and various host- and disease-related variables.
Included were 1250 participants. Mean follow-up for determination of mortality was 6.1 years. Smaller CRAE was related to increased age (P < .001) and hypertension (P < .001); larger CRAE was related to lower hematocrit (P = .002). Larger CRAE and CRVE were associated with black race (P < .001). Larger CRVE was related to smoking (P = .004); smaller CRVE was related to age (P < .001) and higher mean corpuscular volume (P = .001). We observed the following relationships with AIDS-associated factors: smaller CRAE and larger CRVE with history of highly active antiretroviral therapy (HAART; P < .001); and larger CRAE with lower CD4+ T lymphocyte count (P = .04). We did not identify independent relationships with human immunodeficiency virus RNA blood levels. There was a 12% (95% CI, 2%-21%) increase in mortality risk per quartile of decreasing AVR (P = .02).
Variations in retinal vascular caliber are associated with AIDS-specific factors and are markers for increased mortality risk. Relationships are consistent with the hypothesis that the vasculature is altered by known atherogenic effects of chronic HAART or the prolonged inflammatory state associated with AIDS.
American journal of ophthalmology 03/2012; 153(3):434-444.e1. · 3.83 Impact Factor
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ABSTRACT: To evaluate relationships between retinal vessel caliber and tests of visual function among people with AIDS.
Longitudinal, observational cohort study.
We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Visual function was evaluated with best-corrected visual acuity, Goldmann perimetry, automated perimetry (Humphrey Field Analyzer), and contrast sensitivity (CS) testing. Semi-automated grading of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, sought independent relationships between indices and visual function variables.
Included were 1250 participants. Smaller AVR was associated with reduced visual field by Goldmann perimetry (P = .003) and worse mean deviation (P = .02) on automated perimetry and possibly with worse pattern standard deviation (PSD) on automated perimetry (P = .06). There was a weak association between smaller AVR and worse CS (P = .07). Relationships were independent of antiretroviral therapy and level of immunodeficiency (CD4+ T lymphocyte count, human immunodeficiency virus [HIV] RNA blood level). On longitudinal analysis, retinal vascular indices at baseline did not predict changes in visual function.
Variation in retinal vascular indices is associated with abnormal visual function in people with AIDS, manifested by visual field loss and possibly by reduced CS. Relationships are consistent with the hypothesis that HIV-related retinal vasculopathy is a contributing factor to vision dysfunction among HIV-infected individuals. Longitudinal studies are needed to determine whether changes in indices predict change in visual function.
American journal of ophthalmology 03/2012; 153(3):428-433.e1. · 3.83 Impact Factor
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ABSTRACT: To characterize the clinical manifestations of cytomegalovirus (CMV) retinitis in northern Thailand.
Prospective, observational, cross-sectional study.
We recorded characteristics of 52 consecutive patients newly diagnosed with CMV retinitis at a tertiary university-based medical center in northern Thailand. Indirect ophthalmoscopy by experienced ophthalmologists was supplemented with fundus photography to determine the proportion of eyes with various clinical features of CMV retinitis.
Of the 52 patients with CMV retinitis, 55.8% were female. All were HIV-positive. The vast majority (90.4%) had started antiretroviral therapy. CMV retinitis was bilateral in 46.2% of patients. Bilateral visual acuity worse than 20/60 was observed in 23.1% of patients. Of 76 eyes with CMV retinitis, 61.8% had zone I disease and 21.6% had lesions involving the fovea. Lesions larger than 25% of the retinal area were observed in 57.5% of affected eyes. CMV retinitis lesions commonly had marked or severe border opacity (47.4% of eyes). Vitreous haze often was present (46.1% of eyes). Visual impairment was more common in eyes with larger retinitis lesions. Retinitis lesion size, used as a proxy for duration of disease, was associated with fulminant appearance (odds ratio, 1.24; 95% confidence interval, 1.01 to 1.51) and marked or severe border opacity (odds ratio, 1.36; 95% confidence interval, 1.11 to 1.67). Based on lesion size, retinitis preceded antiretroviral treatment in each patient.
Patients seeking treatment at a tertiary medical center in northern Thailand had advanced CMV retinitis, possibly because of delayed diagnosis. Earlier screening and treatment of CMV retinitis may limit progression of disease and may prevent visual impairment in this population.
American journal of ophthalmology 01/2012; 153(5):923-931.e1. · 3.83 Impact Factor
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Kevin D Frick,
Lea T Drye,
John H Kempen,
James P Dunn, Gary N Holland,
Paul Latkany,
Narsing A Rao,
H Nida Sen,
Elizabeth A Sugar,
Jennifer E Thorne,
Robert C Wang,
Janet T Holbrook
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ABSTRACT: To evaluate the associations between visual acuity and self-reported visual function; visual acuity and health-related quality of life (QoL) metrics; a summary measure of self-reported visual function and health-related QoL; and individual domains of self-reported visual function and health-related QoL in patients with uveitis.
Best-corrected visual acuity, vision-related functioning as assessed by the NEI VFQ-25, and health-related QoL as assessed by the SF-36 and EuroQoL EQ-5D questionnaires were obtained at enrollment in a clinical trial of uveitis treatments. Multivariate regression and Spearman correlations were used to evaluate associations between visual acuity, vision-related function, and health-related QoL.
Among the 255 patients, median visual acuity in the better-seeing eyes was 20/25, the vision-related function score indicated impairment (median, 60), and health-related QoL scores were within the normal population range. Better visual acuity was predictive of higher visual function scores (P ≤ 0.001), a higher SF-36 physical component score, and a higher EQ-5D health utility score (P < 0.001). The vision-specific function score was predictive of all general health-related QoL (P < 0.001). The correlations between visual function score and general quality of life measures were moderate (ρ = 0.29-0.52).
The vision-related function score correlated positively with visual acuity and moderately positively with general QoL measures. Cost-utility analyses relying on changes in generic healthy utility measures will be more likely to detect changes when there are clinically meaningful changes in vision-related function, rather than when there are only changes in visual acuity. (ClinicalTrials.gov number, NCT00132691.).
Investigative ophthalmology & visual science 01/2012; 53(3):1169-76. · 3.43 Impact Factor
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ABSTRACT: To investigate relationships between contrast sensitivity (CS), color vision, and retinal nerve fiber layer (RNFL) among people with human immunodeficiency virus (HIV) infection; to evaluate the effect of time since diagnosis of HIV infection on RNFL thickness.
Noninterventional cross-sectional study.
We evaluated 102 eyes of 57 HIV-infected individuals without ocular opportunistic infections. Peripapillary RNFL thickness was determined with spectral-domain optical coherence tomography in 4 quadrants. CS was measured with the Pelli-Robson technique (expressed as logCS); color vision was measured with the Lanthony desaturated 15-hue technique (expressed as color confusion index [C-index], with higher scores indicating worse color vision). Correlations between values were assessed using Spearman correlation coefficients.
Median RNFL thickness (average of 4 quadrants) was 102.9 μm (range, 75.0-134.7 μm). Median logCS was 1.90 (range, 1.25-1.95). Median C-index was 1.58 (range, 0.96-4.07). Temporal RNFL thickness was correlated with logCS (r=0.295, P=.003) and C-index (r=-0.338, P=.0005). Time since diagnosis of HIV infection was shorter for those with thick average RNFL than for those with thin average RNFL (P=.18).
Both worse CS and worse color vision are correlated with thinning of the temporal RNFL, with possible threshold effects. Increased prevalences of abnormal CS and abnormal color vision in this population are therefore likely attributable to neuroretinal compromise. This pattern of structural and functional losses may reflect preferential damage to small-caliber axons in the maculopapillary bundle, possibly associated with mitochondrial dysfunction, providing a potential disease mechanism for HIV-associated "neuroretinal disorder."
American journal of ophthalmology 01/2012; 153(4):734-42, 742.e1. · 3.83 Impact Factor
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The British journal of ophthalmology 12/2011; · 2.92 Impact Factor
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Archives of ophthalmology 11/2011; 129(11):1507-8. · 3.86 Impact Factor
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Somsanguan Ausayakhun,
Alison H Skalet,
Choeng Jirawison,
Sakarin Ausayakhun,
Jeremy D Keenan,
Claire Khouri,
Khang Nguyen,
Partho S Kalyani,
David Heiden, Gary N Holland,
Todd P Margolis
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ABSTRACT: To determine the feasibility of remote diagnostic screening for cytomegalovirus (CMV) retinitis among HIV patients in northern Thailand.
Prospective, observational cross-sectional study.
One hundred eighty-two eyes from 94 consecutive patients with HIV seen in 2008 and 2009 at a tertiary university-based medical center were photographed using a digital retinal camera. Individual and composite images were uploaded to a secure web site. Three expert graders accessed the electronic images and graded each image for signs of CMV retinitis. Results of remote expert grading were compared with on-site patient examination by local expert ophthalmologists.
On-site ophthalmologists diagnosed CMV retinitis in 89 (48.9%) of 182 eyes. Trained ophthalmic photographers obtained digital retinal images for all 182 eyes. As compared with the on-site examinations, the sensitivity for detecting CMV retinitis by remote readers using composite retinal images ranged from 89% to 91%. The specificity for detecting CMV retinitis by remote readers ranged from 85% to 88%. Intrarater reliability was high, with each grader achieving a κ value of 0.93. Interrater reliability among the 3 graders also was high, with a κ value of 0.86.
Remote diagnostic screening for CMV retinitis among HIV-positive patients may prove to be a valuable tool in countries where the burden of HIV exceeds the capacity of the local eye care providers to screen for ocular opportunistic infections.
American journal of ophthalmology 08/2011; 152(6):1053-1058.e1. · 3.83 Impact Factor
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Retina (Philadelphia, Pa.) 04/2011; 31(6):1224-30. · 2.93 Impact Factor
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ABSTRACT: Toxoplasmic retinochoroiditis may recur months or years after the primary infection. Rupture of dormant cysts in the retina is the accepted hypothesis to explain recurrence. Here, the authors present evidence supporting the presence of Toxoplasma gondii in the peripheral blood of immunocompetent patients.
Direct observation by light microscopy and by immunofluorescence assay was performed, and results were confirmed by PCR amplification of parasite DNA.
The authors studied 20 patients from Erechim, Brazil, including acute infected patients, patients with recurrent active toxoplasmic retinochoroiditis, patients with old toxoplasmic retinal scars, and patients with circulating IgG antibodies against T gondii and absence of ocular lesions. Blood samples were analysed, and T gondii was found in the blood of acutely and chronically infected patients regardless of toxoplasmic retinochoroiditis.
The results indicate that the parasite may circulate in the blood of immunocompetent individuals and that parasitaemia could be associated with the reactivation of the ocular disease.
The British journal of ophthalmology 03/2011; 95(3):396-400. · 2.92 Impact Factor
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Jean D Vaudaux,
Cristina Muccioli,
Erick R James,
Claudio Silveira,
Spencer L Magargal,
Calvin Jung,
J P Dubey,
Jeffrey L Jones,
Mehmet Z Doymaz,
David A Bruckner,
Rubens Belfort, Gary N Holland,
Michael E Grigg
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ABSTRACT: Multilocus DNA sequencing has identified a nonarchetypal strain of Toxoplasma gondii as the causal agent of a waterborne outbreak in Brazil in 2001. The strain, isolated from a water supply epidemiologically linked to the outbreak, was virulent to mice, and it has previously been identified as BrI. Using a serologic assay that detects strain-specific antibodies, we found that 13 (65%) of 20 individuals who were immunoglobulin (Ig) M positive during the outbreak possessed the same serotype as mice infected with the purported epidemic strain. The remaining 7 individuals, plus additional IgM-negative, IgG-positive individuals, possessed 1 of 4 novel serotypes, the most common of which matched the serotype of mice infected with strains isolated from chickens foraging near the outbreak site. The latter strains likely reflect the genetic diversity of T. gondii circulating in highly endemic regions of Brazil. The serotyping assay proved a useful tool for identification of specific individuals infected with the outbreak agent.
The Journal of Infectious Diseases 10/2010; 202(8):1226-33. · 6.41 Impact Factor
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ABSTRACT: To determine incidence and risk factors for graft failure following penetrating keratoplasty (PK) in eyes with Ahmed valves (AV).
Retrospective, observational cohort study.
Patients who underwent PK after AV implantation (both performed at our institution through 2004) were studied. Intervals to graft failure (defined as either dysfunction [stromal thickening with retention of clarity] or decompensation [central microcystic edema or loss of clarity]) were analyzed using Kaplan-Meier technique. Risk factors for graft failure were analyzed using Cox proportional hazard models.
Included were 77 eyes (77 patients; first procedure 1993). Following PK, 40 eyes (52%) required increased numbers of glaucoma medications; 10 eyes (13%) required additional glaucoma drainage device(s). Graft failure at 1, 2, and 3 years was 42.4% (95% confidence interval: 32.0%-54.6%), 57.1% (45.6%-69.1%), and 59.1% (47.5%-71.2%), respectively. Prior PK (HR 2.38, P = .006) and stromal vessels (HR 2.90, P = .0005) were associated with increased risk of graft failure. Use of glaucoma medications (HR 0.27, P = .009) and evidence of lower intraocular pressures (IOP) during follow-up (excluding hypotony; HR 0.92, P = .010) were associated with reduced risk of graft failure. Endothelial rejection episodes were observed in 13 eyes (17%); however, rejection was not a risk factor for graft failure (P = .98).
Long-term survival of corneal grafts is poor in eyes with AV. The majority of graft failures are associated with progressive loss of endothelial function, without observed immunologic rejection. Despite the presence of an AV, escalation in glaucoma therapy often follows PK; graft failure may be related to poor IOP control.
American journal of ophthalmology 08/2010; 150(2):169-78. · 3.83 Impact Factor
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ABSTRACT: To investigate the relationship between contrast sensitivity (CS) and mortality among people with acquired immunodeficiency syndrome (AIDS); and to explore the hypothesis that abnormal CS is a marker of systemic, life-threatening microvascular disease.
Longitudinal, observational cohort study.
We evaluated 3395 eyes of 1706 individuals enrolled in the Longitudinal Study of the Complications of AIDS (1998-2008). CS was evaluated as a risk factor for death, and was compared to the presence of systemic diseases characterized by microvasculopathy (diabetes, cardiovascular disease, stroke, renal disease) and to laboratory markers of those diseases. Abnormal CS was defined as logCS <1.5 (lower 2.5th percentile for a normal control population).
CS was abnormal in 284 of 1691 (16.8%) study participants at enrollment. There was a positive relationship between the presence of abnormal CS at study entry and mortality (relative risk 2.0, 95% confidence interval 1.7-2.3, P < .0001). Abnormal CS was related to the presence of cardiovascular disease, stroke, and renal disease (all P values <or= .01), but abnormal CS remained associated with death even after adjustment for these diseases and for other known predictors of death among people with AIDS. Diseases characterized by microvasculopathy were more often identified as causes of death among individuals with abnormal CS than among those with normal CS, although the strength of the association was moderate (P = .06).
Abnormal CS among people with AIDS is associated with increased mortality, and is independent of other risk factors for death that are monitored routinely. The relationship may indicate life-threatening microvascular disease in other organs.
American journal of ophthalmology 05/2010; 149(5):807-16. · 3.83 Impact Factor
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ABSTRACT: Toxoplasmosis is the most common retinal infection in the United States, and it can severely impact vision. We used data from population-based studies, outbreaks, and the U.S. census to estimate the burden of Toxoplasma gondii infection and ocular toxoplasmosis. We estimate that 1,075,242 persons are infected with T. gondii, 21,505 persons have ocular lesions (both asymptomatic and symptomatic), and 4,839 (range = 2,150-7,527) persons develop symptomatic ocular toxoplasmosis each year in the United States. Toxoplasmosis contributes a significant burden to eye disease in the United States.
The American journal of tropical medicine and hygiene 03/2010; 82(3):464-5. · 2.59 Impact Factor
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ABSTRACT: To describe the characteristics and course of late varicella-zoster virus (VZV) dendriform keratitis in patients with histories of herpes zoster ophthalmicus (HZO); to describe responses of corneal lesions to antiviral treatment; and to investigate risk factors for recurrence.
Retrospective case series.
Included were patients known to have 1 or more episodes of dendriform lesions beginning at least 2 weeks after HZO in 2 academic practices. Epithelial lesions were evaluated for the presence of VZV DNA by a polymerase chain reaction assay. Demographic, medical, and ophthalmic data were collected for each episode. Responses to treatment with antiviral medications were evaluated. Cumulative risk of recurrence was determined using Kaplan-Meier analysis; potential risk factors for recurrence (age, systemic disease, lesion characteristics, corticosteroids) were evaluated using univariate Cox proportional hazard models.
We identified 20 patients (14 women; median age, 65 years) who met inclusion criteria. Dendriform lesions were pleomorphic with thickened, opaque epithelium. Seven patients had systemic diseases characterized by altered immune function. VZV DNA was identified in 15 of 16 cases tested, and all lesions responded to antiviral therapy. The 1-year incidence of first recurrence was 95.8 lesions per 100 person-years of follow-up. Patients had multiple recurrences, but risk of recurrence appeared to decrease over time. No statistically significant risk factors for recurrence were identified.
Late dendriform lesions associated with HZO are foci of productive VZV infection. Lesions can be treated effectively with topical or systemic antiviral agents. Patients can have multiple recurrences of dendriform lesions despite treatment.
American journal of ophthalmology 11/2009; 149(2):214-220.e3. · 3.83 Impact Factor
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ABSTRACT: Purpose: To describe a keratopathy in patients with the human immunodeficiency virus (HIV) infection. Methods: Retrospective review of ophthalmic and medical records, including laboratory evaluations, of seven patients with HIV infection and posterior intracorneal opacities. Results: Each patient had a bilateral peripheral keratopathy located at the level of the Descemet membrane that was unassociated with intraocular inflammation. All patients were receiving highly active antiretroviral therapy (HAART). All patients had elevations in their CD4+ T-lymphocyte counts due to HAART prior to presenting with the corneal opacities. Five of the seven patients had elevated serum cholesterol, triglycerides, or both. Best-corrected visual acuity was 20/25 or better in six of the seven patients at the time of diagnosis, and vision remained stable through the follow-up period in all patients (median follow-up: 25 months; range: 14–82 months). The corneal opacities remained unchanged in all seven over the follow-up period. Conclusion: These patients have a bilateral keratopathy that appears to be non-progressive and has no effect on visual acuity.
07/2009; 13(1):25-31.
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Gary N Holland
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ABSTRACT: The influence of patient age on various features of ocular toxoplasmosis has been a subject of study for many years. The age at which Toxoplasma gondii infection occurs in different populations is related to socioeconomic factors and studies suggest that ocular toxoplasmosis is a more severe disease at the extremes of age. The prevalence of ocular involvement is markedly different between individuals with congenital and those with post-natally acquired infections. Even among those with post-natally acquired infections, age influences the risk and timing of ocular involvement. The severity of toxoplasmic retinochoroiditis (in terms of lesion size, location and associated inflammation) is also affected by patient age at the time of initial infection or recurrence. The risk of recurrent toxoplasmic retinochoroiditis is influenced by age at the time of initial infection and age at most recent episode of active disease. Understanding of relationships between ocular toxoplasmosis and patient age is incomplete; evidence has often been indirect and in some cases conflicting. The influence of patient age on ocular toxoplasmosis should be studied in a systematic manner to provide a better understanding of disease mechanisms and to provide clinical information that can used to establish better strategies for disease treatment and prevention.
Memórias do Instituto Oswaldo Cruz 04/2009; 104(2):351-7. · 2.15 Impact Factor
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ABSTRACT: To describe clinical features of chronic anterior uveitis in children at presentation to a referral center (baseline); to identify relationships between demographic, medical, and ophthalmic factors at baseline; and to determine baseline factors that predict new complications and vision loss during follow-up.
Retrospective case series.
Studied were involved eyes of all children (age < or =16 years at disease onset) with chronic anterior uveitis who were examined by 1 clinician from 1993 through 2006. Cross-sectional analyses compared baseline findings. Relationships between potential risk factors and incident adverse events (new complications, vision loss) were studied by Kaplan-Meier and Cox proportional hazards regression models.
There were 115 patients (200 eyes) who met inclusion criteria. Follow-up (n = 83 patients) ranged from 0.4 to 157.5 months (median, 23.5 months). There were numerous strong relationships between 8 defined complications at baseline in pairwise comparisons. Flare was the inflammatory sign most consistently associated with complications at baseline. Baseline factors that predicted new complications during follow-up included age < or =3 years, elevated cells, elevated flare, keratic precipitates, signs of intermediate uveitis, and papillitis (all P < .043); factors that predicted vision loss included male gender, increased flare, signs of intermediate uveitis, papillitis, and baseline complications (all P < .015). Not related to new complications were presence of juvenile idiopathic uveitis and immunomodulatory therapy.
Chronic anterior uveitis in children is associated with various vision-threatening complications that occur in combinations. Complications develop early in the disease course. Patients with more severe disease at presentation are at increased risk of additional adverse events.
American journal of ophthalmology 02/2009; 147(4):667-678.e5. · 3.83 Impact Factor
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Gary N Holland,
Rubens Belfort,
Jean-Paul Dernouchamps,
Rudolph Franklin,
Anne-Catherine Martenet,
Robert A Nozik,
Robert B Nussenblatt,
Shigeaka Ohno,
Gerassimos Palimeris,
K Matti Saari,
Ivan R Schwab,
Antonio G Secchi,
Ronald E Smith,
Khalid F Tabbara,
Howard H Tessler
American journal of ophthalmology 01/2009; 146(6):795-8. · 3.83 Impact Factor
