Verteporfin photodynamic therapy cohort study:report 1: effectiveness and factors influencing outcomes

Purpose - To compare the visual outcomes after verteporfin photodynamic therapy (VPDT) administered in routine clinical practice with those observed in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) trials and to quantify the effects of clinically important baseline covariates on outcome. Design - A prospective longitudinal study of patients treated with VPDT in 45 ophthalmology departments in the United Kingdom with expertise in the management of neovascular age-related macular degeneration (nAMD). Participants - Patients with wholly or predominantly classic choroidal neovascularization (CNV) of any cause with a visual acuity =20/200 in the eye to be treated. Methods - Refracted best-corrected visual acuity (BCVA) and contrast sensitivity were measured in VPDT-treated eyes at baseline and subsequent visits. Eyes were retreated at 3 months if CNV was judged to be active. Baseline angiograms were graded to quantify the percentages of classic and occult CNV. Treated eyes were categorized as eligible or ineligible for TAP, or unclassifiable. Main Outcome Measures - Best-corrected visual acuity and contrast sensitivity during 1 year of follow-up after initial treatment. Results - A total of 7748 treated patients were recruited. Data from 4043 patients with a diagnosis of nAMD were used in the present analysis. Reading center determination of lesion type showed that 87% were predominantly classic CNV. Eyes received 2.4 treatments in year 1 and 0.4 treatments in year 2. Deterioration of BCVA over 1 year was similar to that observed in the VPDT arms of the TAP trials and was not influenced by TAP eligibility classification. Best-corrected visual acuity deteriorated more quickly in current smokers; with increasing proportion of classic CNV, increasing age, and better baseline BCVA; and when the fellow eye was the better eye.

Sequential Morphological Changes in the CNV Net after Intravitreal Anti-VEGF Evaluated with OCT Angiography

PURPOSE: To assess and describe sequential morphological changes in the choroidal neovascularization (CNV) net using optical coherence tomography angiography (OCTA) in patients undergoing treatment with intravitreal antivascular endothelial growth factor (VEGF). METHODS: Prospective cohort study. OCTA was performed sequentially: before (t0), 1 h (t1), 1 week (t2) and 1 month after the injection (t3), using Avanti RTVue XR equipped with the AngioVue® software (Optovue, Calif., USA). All images were classified by two independent graders. RESULTS: Ten eyes of 10 patients, with a mean age of 72.4 ± 10.5 years, were included. CNV morphology was described as tree-like in 5 eyes, glomerular in 1 and fragmented in 4. A fibrovascular capsule surrounding the CNV net was found in 4 eyes and a feeder trunk was noticed in 6. No changes were observed at t1. Loss of peripheral capillaries, vessel fragmentation and decreased vessel density were evident in 8 eyes at t2. The CNV capillary density and the peripheral anastomosis increased in all of these at t3. Two eyes remained unchanged through the whole length of follow-up. CONCLUSIONS: Significant changes in the CNV net can be observable in OCTA at least 1 week after intravitreal anti-VEGF. The safety of frequent examinations may provide a method of gauging treatment effects.

Sequential Morphological Changes in the CNV Net after Intravitreal Anti-VEGF Evaluated with OCT Angiography

PURPOSE: To assess and describe sequential morphological changes in the choroidal neovascularization (CNV) net using optical coherence tomography angiography (OCTA) in patients undergoing treatment with intravitreal antivascular endothelial growth factor (VEGF). METHODS: Prospective cohort study. OCTA was performed sequentially: before (t0), 1 h (t1), 1 week (t2) and 1 month after the injection (t3), using Avanti RTVue XR equipped with the AngioVue® software (Optovue, Calif., USA). All images were classified by two independent graders. RESULTS: Ten eyes of 10 patients, with a mean age of 72.4 ± 10.5 years, were included. CNV morphology was described as tree-like in 5 eyes, glomerular in 1 and fragmented in 4. A fibrovascular capsule surrounding the CNV net was found in 4 eyes and a feeder trunk was noticed in 6. No changes were observed at t1. Loss of peripheral capillaries, vessel fragmentation and decreased vessel density were evident in 8 eyes at t2. The CNV capillary density and the peripheral anastomosis increased in all of these at t3. Two eyes remained unchanged through the whole length of follow-up. CONCLUSIONS: Significant changes in the CNV net can be observable in OCTA at least 1 week after intravitreal anti-VEGF. The safety of frequent examinations may provide a method of gauging treatment effects.

Caracterización y prevalencia del compromiso ocular en pacientes con enfermedad autoinmune y autoinflamatoria en un centro de referencia reumatológica en Colombia entre los años 2000 a 2015

RESUMEN Objetivo: Estimar la prevalencia de las diferentes enfermedades oftalmológicas que aparecen en el contexto de una enfermedad autoinmune (EAI) en pacientes de un centro de referencia reumatológica en Colombia, según características clínicas y sociodemográficas durante un período de 15 años, comprendido entre los años 2000 a 2015. Métodos: Se realizó un estudio descriptivo, observacional de prevalencia. El tipo de muestreo fue aleatorio estratificado con asignación proporcional en el programa Epidat 3.4. Los datos se analizaron en el programa SPSS v22.0 y se realizó análisis univariado de las variables categóricas, para las variables cuantitativas se realizaron medidas de tendencia central. Resultados: De 1640 historias clínicas revisadas, se encontraron 634 pacientes (38,65%) con compromiso ocular. Si excluimos los pacientes con SS, que por definición presentan ojo seco, 222 pacientes (13,53%) presentaron compromiso oftalmológico. Del total de pacientes, el 83,3% fueron mujeres. La AR fue la enfermedad autoinmune con mayor compromiso oftalmológico con 138 pacientes (62,2%), y en último lugar la sarcoidosis con 1 solo paciente afectado. La QCS fue la manifestación más común en todos los grupos diagnósticos de EAI, con 146 pacientes (63,5%). De 414 pacientes con Síndrome de Sjögren (SS) y QCS 8 presentaron compromiso ocular adicional, siendo la uveítis la segunda patología ocular asociada en pacientes con SS y la primera causa en las espondiloartropatias (71,4 %). Los pacientes con catarata (4,1%) presentaron la mayor prevalencia de uso de corticoide (88.8%). De 222 pacientes, 28 (12,6%) presentaron uveítis. Del total de pacientes, 16 (7,2%) presentaron maculopatía por antimalaráricos y 6 (18,75%) de los pacientes con LES. Los ANAS se presentaron en el 100% los pacientes con trastorno vascular de la retina. Los pacientes con epiescleritis presentaron la mayor proporción de positivización de anticuerpos anti-DNA. La EAI que más presentó epiescleritis fue LES con 4 pacientes (12,5%) El 22% de paciente con anticuerpos anti-RNP presentaron escleritis y 32,1% de los pacientes con uveítis presentaron HLA-B27 positivo. Las manifestaciones oftalmológicas precedieron a las sistémicas entre un 11,1% y un 33,3% de los pacientes. Conclusión: Las enfermedades oculares se presentan con frecuencia en los pacientes colombianos con EAI (38.65%), siendo la AR la enfermedad con mayor compromiso ocular (62,2%) y la QCS la enfermedad ocular con mayor prevalencia en todas las EAI (63,5%). La uveítis se presentó en 28 pacientes (12,6%). Las manifestaciones oftalmológicas pueden preceder a las sistémicas. El examen oftalmológico debe ser incluido en los pacientes con EAI, por ser la enfermedad ocular una comorbilidad frecuente. Adicionalmente, los efectos oftalmológicos de las medicaciones sistémicas utilizadas en EAI deben ser estrechamente monitorizados, durante el curso del tratamiento.

Choroidal osteoma: evidence of progression and decalcification over 20 years

Choroidal osteoma is a rare, benign, ossifying tumour of the choroid of unknown aetiology. In contrast to other types of intraocular ossification, choroidal osteoma is found typically in young healthy females in the second or third decades of life with no history of systemic or ocular disease. Choroidal osteoma is a deep, pale yellow lesion with distinct geographic borders at the juxtapapillary or macular region, with branching 'spider' vessels on the surface of the tumour. These features should help differentiate choroidal osteoma from other types of intraocular tumour and the diagnosis can be confirmed with ultrasonography and computerised tomography. Here we report an initially unilateral case of choroidal osteoma, which decalcified over 20 years but during the same period the fellow eye also developed a choroidal osteoma to become a bilateral case. Despite the benign nature of the tumour, vision may be compromised by gradual atrophy of the overlying retina, serous retinal detachment, accumulation of sub-retinal fluid and sub-retinal haemorrhage associated with choroidal neovascularisation. Frequent examinations are recommended for patients with choroidal osteoma, for early detection of a subretinal neovascular membrane and potential treatment with laser photocoagulation.

The ratio of VEGF/PEDF expression in bone marrow mesenchymal stem cells regulates neovascularization

Angiogenesis, or neovascularization, is a finely balanced process controlled by pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is a major pro-angiogenic factor, whereas pigment epithelial-derived factor (PEDF) is the most potent natural angiogenesis inhibitor. In this study, the regulatory role of bone marrow stromal cells (BMSCs) during angiogenesis was assessed by the endothelial differentiation potential, VEGF/PEDF production and responses to pro-angiogenic and hypoxic conditions. The in vivo regulation of blood vessel formation by BMSCs was also explored in a SCID mouse model. Results showed that PEDF was expressed more prominently in BMSCs compared to VEGF. This contrasted with human umbilical vein endothelial cells (HUVECs) where the expression of VEGF was higher than that of PEDF. The ratio of VEGF/PEDF gene expression in BMSCs increased when VEGF concentration reached 40 ng/ml in the culture medium, but decreased at 80 ng/ml. Under CoCl2- induced hypoxic conditions, the VEGF/PEDF ratio of BMSCs increased significantly in both normal and angiogenic culture media. There was no expression of endothelial cell markers in BMSCs cultured in either pro-angiogenic or hypoxia culture conditions when compared with HUVECs. The in vivo study showed that VEGF/PEDF expression closely correlated with the degree of neovascularization, and that hypoxia significantly induced pro-angiogenic activity in BMSCs. These results indicate that, rather than being progenitors of endothelial cells, BMSCs play an important role in regulating the neovascularization process, and that the ratio of VEGF and PEDF may, in effect, be an indicator of the pro- or antiangiogenic activities of BMSCs.

Validation of optical low coherence reflectometry retinal and choroidal biometry

To compare measurements of retinal thickness (RT) and choroidal thickness (ChT) obtained with an optical low coherence reflectometry (OLCR) biometer (Lenstar LS 900) with those obtained with a spectral domain optical coherence tomographer (SD OCT) (Copernicus SOCT HR) in young normal subjects.

Using optical coherence tomography for differential diagnosis of a pigmented choroidal lesion

Clinicians regularly face the confronting challenge of differentiating a choroidal naevus from a melanoma. Uveal naevi are a relatively common finding during routine eye examinations: a prevalence of 6.5 per cent has been reported.1 In contrast, malignant melanomata are uncommon, being found in six persons per million population, but they can have devastating implications and consequences.2 Differential diagnoses can be difficult to make with certainty; any additional information that can assist in this process is advantageous...

Retinal and choroidal thickness in myopic anisometropia

PURPOSE: To examine the foveal retinal thickness (RT) and subfoveal choroidal thickness (ChT) between the fellow eyes of myopic anisometropes. METHODS: Twenty-two young (mean age 23 ± 5 years), healthy myopic anisometropes (≥ 1 D spherical equivalent [SEq] anisometropia) without amblyopia or strabismus were recruited. Spectral domain optical coherence tomography (SD-OCT) was used to capture images of the retina and choroid. Customised software was used to register, align and average multiple foveal OCT B-Scan images from each subject in order to enhance image quality. Two independent masked observers then manually determined the RT and ChT at the centre of the fovea from each SD-OCT image, which were then averaged. Axial length was measured using optical low coherence biometry during relaxed accommodation. RESULTS: The mean absolute SEq anisometropia was 1.74 ± 0.95 D and the mean interocular difference in axial length was 0.58 ± 0.41 mm. There was a strong correlation between SEq anisometropia and the interocular difference in axial length (r = 0.90, p < 0.001). Measures of RT and ChT were highly correlated between the two observers (r = 0.99 and 0.97 respectively) and in close agreement (mean inter-observer difference: RT 1.3 ± 2.2 µm, ChT 1.5 ± 13.7 µm). There was no significant difference in RT between the more (218 ± 18 µm) and less myopic eyes (215 ± 18 µm) (p > 0.05). However, the mean subfoveal ChT was significantly thinner in the more myopic eye (252 ± 46 µm) compared to the fellow, less myopic eye (286 ± 58 µm) (p < 0.001). There was a moderate correlation between the interocular difference in ChT and the interocular difference in axial length (r = -0.50, p < 0.01). CONCLUSIONS: Foveal RT was similar between the fellow eyes of myopic anisometropes; however, the subfoveal choroid was significantly thinner in the more myopic (longer) eye of our anisometropic cohort. The interocular difference in ChT correlated with the magnitude of axial anisometropia.

Axial length and choroidal thickness changes accompanying prolonged accommodation in myopes and emmetropes

The time course of elongation and recovery of axial length associated with a 30 minute accommodative task was studied using optical low coherence reflectometry in a population of young adult myopic (n = 37) and emmetropic (n = 22) subjects. Ten of the 59 subjects were excluded from analysis either due to inconsistent accommodative response, or incomplete anterior biometry data. Those subjects with valid data (n = 49) were found to exhibit a significant axial elongation immediately following the commencement of a 30 minute, 4 D accommodation task, which was sustained for the duration of the task, and ¬was evident to a lesser extent immediately following task cessation. During the accommodation task, on average, the myopic subjects exhibited 22 ± 34 µm, and the emmetropic subjects 6 ± 22 µm of axial elongation, however the differences in axial elongation between the myopic and emmetropic subjects were not statistically significant (p = 0.136). Immediately following the completion of the task, the myopic subjects still exhibited an axial elongation (mean magnitude 12 ± 28 µm), that was significantly greater (p < 0.05) than the changes in axial length observed in the emmetropic subjects (mean change -3 ± 16 µm). Axial length had returned to baseline levels 10 minutes after completion of the accommodation task. The time for recovery from accommodation-induced axial elongation was greater in myopes, which may reflect differences in the biomechanical properties of the globe associated with refractive error. Changes in subfoveal choroidal thickness were able to be measured in 37 of the 59 subjects, and a small amount of choroidal thinning was observed during the accommodation task that was statistically significant in the myopic subjects (p < 0.05). These subfoveal choroidal changes could account for some but not all of the increased axial length during accommodation.

Monocular myopic defocus and daily changes in axial length and choroidal thickness of human eyes

Recent research indicates that brief periods (60 minutes) of monocular defocus lead to small but significant changes in human axial length. However, the effects of longer periods of defocus on the axial length of human eyes are unknown. We examined the influence of a 12 hour period of monocular myopic defocus on the natural daily variations occurring in axial length and choroidal thickness of young adult emmetropes. A series of axial length and choroidal thickness measurements (collected at ~3 hourly intervals, with the first measurement at ~9 am and the final measurement at ~9 pm) were obtained for 13 emmetropic young adults over three consecutive days. The natural daily rhythms (Day 1, baseline day, no defocus), the daily rhythms with monocular myopic defocus (Day 2, defocus day, +1.50 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, recovery day, no defocus) were all examined. Significant variations over the course of the day were observed in both axial length and choroidal thickness on each of the three measurement days (p<0.0001). The magnitude and timing of the daily variations in axial length and choroidal thickness were significantly altered with the monocular myopic defocus on day 2 (p<0.0001). Following the introduction of monocular myopic defocus, the daily peak in axial length occurred approximately 6 hours later, and the peak in choroidal thickness approximately 8.5 hours earlier in the day compared to days 1 and 3 (with no defocus). The mean amplitude (peak to trough) of change in axial length (0.030 ± 0.012 on day 1, 0.020 ± 0.010 on day 2 and 0.033 ± 0.012 mm on day 3) and choroidal thickness (0.030 ± 0.007 on day 1, 0.022 ± 0.006 on day 2 and 0.027 ± 0.009 mm on day 3) were also significantly different between the three days (both p<0.05). The introduction of monocular myopic defocus disrupts the daily variations in axial length and choroidal thickness of human eyes (in terms of both amplitude and timing) that return to normal the following day after removal of the defocus.

Retinal and choroidal thickness in myopic anisometropia

Purpose: To compare the retinal thickness (RT) and choroidal thickness (ChT) between the fellow eyes of non-amblyopic myopic anisometropes. Methods: The eyes of 22 non-amblyopic myopic anisometropes (1 D spherical equivalent refraction [SER] anisometropia) were examined using spectral domain optical coherence tomography (SD-OCT). Customised software was used to register, align and average multiple foveal OCT B-Scan images from each subject in order to enhance image quality. Two independent masked observers manually determined the RT and ChT from each SD-OCT image up to 2.5 mm nasal and temporal to the fovea. Axial length (AXL) was measured using optical low coherence biometry during relaxed accommodation. Results: The mean SER anisometropia was 1.74 ± 0.95 D and the mean interocular AXL difference was 0.58 ± 0.41 mm. There was no significant difference in foveal RT between the fellow eyes (P > 0.05). Mean subfoveal ChT was significantly thinner in the more myopic eye (252 ± 46 μm compared to the fellow, less myopic eye (286 ± 58 μm) (P < 0.001). There was a moderate correlation between the interocular difference in subfoveal ChT and the interocular difference in AXL (r = -0.50, P < 0.01). Asian anisometropes displayed more regionally symmetrical (nasal-temporal)interocular differences in ChT profile compared to Caucasians. Conclusions: RT was similar between the fellow eyes of myopic anisometropes; however, the subfoveal choroid was significantly thinner in the more myopic (longer) eye of this anisometropic cohort. The interocular asymmetry in ChT correlated with the interocular difference in AXL.

Choroidal thickness in childhood

Purpose To examine choroidal thickness (ChT) and its spatial distribution across the posterior pole in pediatric subjects with normal ocular health and minimal refractive error. Methods ChT was assessed using spectral domain optical coherence tomography (OCT) in 194 children aged between 4-12 years, with spherical equivalent refractive errors between +1.25 and -0.50 DS. A series of OCT scans were collected, imaging the choroid along 4 radial scan lines centered on the fovea (each separated by 45°). Frame averaging was used to reduce noise and enhance chorio-scleral junction visibility. The transverse scale of each scan was corrected to account for magnification effects associated with axial length. Two independent masked observers manually segmented the OCT images to determine ChT at foveal centre, and averaged across a series of perifoveal zones over the central 5 mm. Results The average subfoveal ChT was 330 ± 65 µm (range 189-538 µm), and was significantly influenced by age (p=0.04). The ChT of the 4 to 6 year old age group (312 ± 62 µm) was significantly thinner compared to the 7 to 9 year olds (337 ± 65 µm, p<0.05) and bordered on significance compared to the 10 to 12 year olds (341 ± 61 µm, p=0.08). ChT also exhibited significant variation across the posterior pole, being thicker in more central regions. The choroid was thinner nasally and inferiorly compared to temporally and superiorly. Multiple regression analysis revealed age, axial length and anterior chamber depth were significantly associated with subfoveal ChT (p<0.001). Conclusions ChT increases significantly from early childhood to adolescence. This appears to be a normal feature of childhood eye growth.