Macular Degeneration: Sadda SR

Margalit E, Sadda SR. · Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. · Artif Organs. · Pubmed #14616515 No free full text.

Abstract: A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device.

Humayun MS, de Juan E, del Cerro M, Dagnelie G, Radner W, Sadda SR, del Cerro C. · Department of Ophthalmology, Wilmer Ophthalmological Institute, the Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. · Invest Ophthalmol Vis Sci. · Pubmed #10967070 links to  free full text

Abstract: PURPOSE: A pilot study of human neural retinal transplantation was undertaken to investigate three major issues: whether a safe surgical procedure could be devised for transplantation of neural retinal tissue into the subretinal space, whether the transplant would be accepted in the subretinal space, and whether an improvement in vision could be achieved. METHODS: Eight patients with bare light perception (LP) vision due to retinitis pigmentosa (RP) and one patient with bare LP vision due to advanced neovascular age-related macular degeneration (AMD) received subretinal transplants of human fetal retinal microaggregate suspensions without postoperative systemic immunosuppression. The patient with AMD also received a fetal retinal sheet transplant. The ages of the patients ranged from 31 to 94 years (median, 55 years). The pre- and postoperative evaluations included visual function testing, detailed fundus examinations, fundus photography, fluorescein angiography, macular perimetry using a scanning laser ophthalmoscope (SLO), and full field and focal electroretinograms (ERGs). RESULTS: Three of the eight RP patients demonstrated possible improved light sensitivity during the initial months of follow-up. However, visual improvement disappeared between 3 and 13 months of follow-up. After transplantation, no subject showed any changes in the ERG recordings or SLO macular perimetry relative to their preoperative baseline. No patient experienced a retinal detachment, infection, or extensive bleeding. None of the patients developed retinal vasculitis or intraocular inflammation. In one RP patient, fluorescein angiography and fundus photography documented the formation and maturation of new host retinal vessels in the area of the transplant. CONCLUSIONS: Transplantation of fetal retinal photoreceptor suspensions into the subretinal space was achieved safely in nine subjects. Although a definite positive effect on visual function could not be demonstrated, the apparent high tolerance for graft tissue is promising for future efforts in the field of neural retinal transplantation.

Keane PA, Chang KT, Liakopoulos S, Jivrajka RV, Walsh AC, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of University of Southern California, Los Angeles, California 90033, USA. · Retina. · Pubmed #19289984 No free full text.

Abstract: PURPOSE: To determine the characteristics of patients with neovascular age-related macular degeneration who show initial anatomic improvements on optical coherence tomography in response to treatment with ranibizumab, but who subsequently regress toward their anatomic baseline. METHODS: Data from 50 consecutive patients, receiving ranibizumab therapy for neovascular age-related macular degeneration, were collected. Raw StratusOCT images were analyzed using custom software ("OCTOR"). Changes in volume of neurosensory retina at months 1, 3, and 6 were calculated. Baseline demographic and morphologic characteristics were compared. RESULTS: Forty-two patients (84%) showed a reduction in total retinal volume 1 month after initial treatment with ranibizumab. Of the patients that initially showed a reduction, 16 (38%) maintained this reduction through month 6, whereas 26 patients (62%) demonstrated a subsequent increase in retinal volume. Patients who maintained a reduction in edema received 3.75 +/- 1.18 injections of ranibizumab versus 2.96 +/- 1.34 injections for patients who did not (P = 0.049). Regression of initial anatomic improvements was associated with worsening of visual acuity (r = 0.599, P = 0.002). CONCLUSION: Patients receiving fewer injections of ranibizumab appeared less likely to maintain anatomic improvements achieved following commencement of ranibizumab therapy; regression of these improvements was associated with deterioration in visual acuity.

Keane PA, Liakopoulos S, Jivrajka RV, Chang KT, Alasil T, Walsh AC, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #19264895 No free full text.

Abstract: PURPOSE: To investigate the relationship between automated and manually derived measurements of central retinal thickness from optical coherence tomography (OCT) and to determine the relationship between the foveal center point (FCP) and the foveal central subfield (FCS) in neovascular age-related macular degeneration (AMD). METHODS: Data were collected from 216 patients with newly diagnosed neovascular AMD, who underwent StratusOCT imaging at diagnosis. Raw StratusOCT images for each patient were analyzed with the publicly available custom software OCTOR, which allows accurate manual grading of OCT B-scans. Manually derived central retinal thickness measurements were compared with measurements obtained from automated StratusOCT analysis. Manually obtained measurements of FCP and FCS were also compared. RESULTS: The mean (+/-SD) difference in thickness between automated and manually derived FCP thickness was 7.9 microm (+/-90.8), but the maximum difference was 455 microm. The limits of agreement (95% confidence interval), between automated and manually obtained FCP thicknesses, were -173.7 microm (lower limit) and 189.6 microm (upper limit), with a coefficient of determination (R(2)) of 0.49 (P < 0.001). In contrast, the R(2) for manually derived FCP and manually derived FCS thickness was 0.94 (P < 0.001), with a smaller mean (+/-SD) difference in thickness of 13.8 microm (+/-29.8). CONCLUSIONS: Manual correction of errors in automated OCT segmentation may be necessary for accurate interpretation of anatomic outcomes for clinical trials of neovascular AMD. In addition, although measurement of FCS remains preferable for assessment of central retinal thickness, accurate measurement of FCP may represent an adequate alternative when FCS is unavailable.

Kashani AH, Keane PA, Dustin L, Walsh AC, Sadda SR. · Department of Preventative Medicine, Keck School of Medicine, Doheny Image Reading Center, Doheny Eye Institute, University of Southern California, Los Angeles, CA 90033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #19168893 No free full text.

Abstract: PURPOSE: To use optical coherence tomography (OCT) to quantify intraretinal cystoid spaces (ICSs) and the outer nuclear layer (ONL) in patients with neovascular age-related macular degeneration (AMD) and to investigate the correlation of these parameters with visual acuity. METHODS: StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) images were collected from 53 patients receiving their initial treatment with intravitreous ranibizumab. Images were analyzed with custom software (OCTOR) that allows accurate manual segmentation of OCT B-scans and provides thickness/volume measurements of ICS, ONL, neurosensory retina, pigment epithelial detachments (PEDs), subretinal fluid (SRF), and subretinal tissue (SRT). Univariate and multivariate analyses were used to correlate OCT parameters with best corrected Snellen visual acuity. Reproducibility was assessed with weighted kappa statistics and intraclass correlation coefficients. RESULTS: A multivariate linear regression model with adjusted R(2) showed that ONL volume and SRT thickness significantly correlated with Snellen visual acuity (R(2) = 0.15, P = 0.002 and R(2) = 0.19, P = 0.001, respectively) with an overall model R(2) of 0.34. Adjustment of ONL volume for ICS did not improve correlation with visual acuity, and ICS volume did not independently correlate with visual acuity. Weighted kappa statistics showed excellent intergrader agreement for both ICS and ONL measurements. CONCLUSIONS: The results suggest that an increased total volume of the ONL is associated with decreased visual acuity in neovascular AMD and that the total volume of ICS does not correlate with visual acuity. Although the correlations detected in this study are modest, quantitative subanalysis of OCT images may be of greater clinical relevance in the context of more advanced OCT technology.

Keane PA, Liakopoulos S, Chang KT, Wang M, Dustin L, Walsh AC, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. · Ophthalmology. · Pubmed #18930551 No free full text.

Abstract: PURPOSE: To investigate the relationship between optical coherence tomography (OCT)-derived measurements of retinal morphology and visual acuity in patients with neovascular age-related macular degeneration (AMD). DESIGN: Retrospective cross-sectional study. PARTICIPANTS: A total of 216 consecutive patients (216 eyes) newly diagnosed with neovascular AMD who underwent StratusOCT imaging at the time of diagnosis. METHODS: Best-corrected Snellen visual acuity was recorded for each patient. Raw exported StratusOCT images for each patient were analyzed using publicly available custom software entitled "OCTOR," which allows the precise positioning of prespecified boundaries on individual B-scans. Thickness and volume were calculated for morphologic parameters of interest: neurosensory retina, subretinal fluid, subretinal tissue (SRT), and pigment epithelial detachment. MAIN OUTCOME MEASURES: OCT-derived measurements of retinal morphology and visual acuity. RESULTS: An increased total volume of SRT was correlated with decreased visual acuity (r = 0.370, P<0.0001). Decreased visual acuity was also modestly correlated with increased thickness of the neurosensory retina at the foveal center point (r = 0.245, P = 0.0004). No statistically significant association was detected between visual acuity and the total volume of subretinal fluid or pigment epithelial detachment. The association between visual acuity and both the neurosensory retina and the SRT was stronger for lesions classified as minimally classic or occult on fluorescein angiography. For occult lesions, 20% of the variation in visual acuity could be predicted by a multiple regression model that incorporated age and SRT volume, whereas, for minimally classic lesions, 62% of the variation in visual acuity could be predicted by a multiple regression model that incorporated age, total neurosensory retinal volume, and total SRT volume. CONCLUSIONS: The presence of increased SRT thickness and volume on OCT, and to a lesser extent increased neurosensory retinal thickness and volume, is associated with decreased visual acuity in neovascular AMD. However, because of the complex pathophysiology of neovascular AMD and, in part, the limitations of StratusOCT, these factors only account for a small degree of the variation in visual acuity that these patients exhibit. The detection of stronger correlations between retinal anatomy and visual acuity is likely to require the use of more advanced imaging modalities. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Wu Z, Sadda SR. · Doheny Retina Institute, Doheny Eye Institute, Los Angeles, CA 90033, USA. · Ann Acad Med Singapore. · Pubmed #18695773 links to  free full text

Abstract: INTRODUCTION: We report a case in which intravitreal bevacizumab and ranibizumab appeared to have effects in the contralateral, uninjected eye. CLINICAL PICTURE: An 83-year-old man with macular oedema from branch retinal vein occlusion (BRVO) in the right eye developed neovascular macular degeneration in the left eye. Intravitreal bevacizumab in the left eye improved macular oedema in the right eye temporarily before it recurred. Subsequently, intravitreal ranibizumab in the left eye also resulted in significant reduction of macular oedema in the right eye. OUTCOME: Vision and macular oedema in the right eye improved. CONCLUSION: Bevacizumab and ranibizumab may have therapeutic effects in the uninjected eye, possibly because they may escape from the eye into the systemic circulation.

Keane PA, Liakopoulos S, Chang KT, Heussen FM, Ongchin SC, Walsh AC, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the University of Southern California, 1450 San Pablo Street, DEI 3623, Los Angeles, CA 90033, USA. · Br J Ophthalmol. · Pubmed #18586903 No free full text.

Abstract: AIM: To compare the retinal morphological characteristics of eyes with choroidal neovascularisation (CNV) secondary to pathological myopia versus eyes with CNV secondary to age-related macular degeneration (AMD), using quantitative optical coherence tomography (OCT) subanalysis. METHODS: Twenty-one eyes of 21 patients newly diagnosed as having CNV secondary to pathological myopia, and 43 consecutive cases of eyes with newly diagnosed subfoveal CNV secondary to AMD were retrospectively collected. In all patients, StratusOCT images and fluorescein angiograms (FA) were available for analysis. StratusOCT images were analysed using custom software (termed "OCTOR"), which allowed calculation of the thickness/volume of the neurosensory retina, subretinal fluid (SRF), subretinal tissue (SRT) and pigment epithelial detachments (PEDs). FA images were used to calculate CNV leakage area and CNV lesion size for each eye. RESULTS: The total volume of neurosensory retina in the pathological myopia group was significantly less than in the AMD group (7.10 (SD 0.50) mm3 vs 7.76 (0.93) mm3, p = 0.004). The total volume of SRF in the pathological myopia group was less than in the AMD group, but the difference was not statistically significant (0.33 (1.38) mm3 vs 0.55 (0.82) mm3, p = 0.434). The total volume of SRT in the pathological myopia group was less than in the AMD group, but the difference was not statistically significant (0.16 (0.15) mm3 vs 0.36 (0.60) mm3, p = 0.144). The total volume of PED in the pathological myopia group was markedly less than in the AMD group (0.01 (0.03) mm3 vs 1.09 (1.89) mm3, p<0.001). On FA, the total leakage of CNV in the AMD group was significantly greater than in the pathological myopia group (4.17 (3.29) DAs vs 0.53 (0.58) DAs, p<0.001). CONCLUSIONS: CNV lesions in pathological myopia were associated with considerably less retinal oedema, SRF and SRT compared with CNV associated with AMD. PEDs were almost negligible in myopic lesions compared with AMD. These findings are consistent with previous clinical and angiographic descriptions of myopic CNV as relatively small lesions with modest exudation.

Liakopoulos S, Ongchin S, Bansal A, Msutta S, Walsh AC, Updike PG, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18566473 links to  free full text

Abstract: PURPOSE: To compare the volume of various spaces visible on optical coherence tomography (OCT) images in different angiographic lesion subtypes of neovascular age-related macular degeneration (AMD). METHODS: Sixty-six cases of previously untreated, active subfoveal choroidal neovascularization (CNV) associated with AMD were retrospectively collected. CNV lesions were classified as occult with no classic CNV, minimally classic CNV, predominantly classic CNV, or CNV lesions with associated retinal angiomatous proliferation (RAP). Corresponding OCT image sets were analyzed by trained graders using previously validated custom software that allows manual placement of boundaries on OCT B-scans. Spaces delineated by these boundaries included the neurosensory retina, subretinal fluid, subretinal tissue, and pigment epithelial detachments (PEDs). Volume measurements were calculated by the software and compared among groups. RESULTS: Minimally and predominantly classic CNV membranes demonstrated subretinal tissue on OCT in all cases and appeared to show a significantly greater volume of subretinal tissue than did the occult membranes. Subretinal fluid was present in all the predominantly classic cases. A PED was visible in all the occult CNV cases in our study, demonstrating less retinal thickening and significantly greater PED volumes than minimally and predominantly classic CNV lesions. Lesions associated with RAP showed the highest percentage of cystoid spaces. CONCLUSIONS: OCT and angiography provide complementary information regarding CNV lesions. Quantitative analysis of OCT images allows for an improved understanding of the anatomic characteristics of angiographically defined CNV lesion subtypes.

Keane PA, Liakopoulos S, Ongchin SC, Heussen FM, Msutta S, Chang KT, Walsh AC, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18408176 links to  free full text

Abstract: PURPOSE: To investigate the effects of ranibizumab on retinal morphology in patients with neovascular age-related macular degeneration (AMD) using optical coherence tomography (OCT) quantitative subanalysis. METHODS: Data from 95 patients receiving intravitreal ranibizumab for neovascular AMD were collected. StratusOCT images were analyzed using custom software that allows precise positioning of prespecified boundaries on every B-scan. Changes in thickness/volume of the retina, subretinal fluid (SRF), subretinal tissue (SRT), and pigment epithelial detachments (PEDs) at week 1 and at months 1, 3, 6, and 9 after treatment were calculated. RESULTS: Total retinal volume reached its nadir at month 1, with an average reduction of 0.43 mm(3) (P < 0.001). By month 9, this initial change had been reduced to a mean reduction of 0.32 mm(3) (P = 0.0011). Total SRF volume reached its lowest level by month 1, with an average reduction of 0.24 mm(3) (P < 0.001). This reduction lessened subsequently, to 0.18 mm(3), by month 9. There was an average 0.3-mm(3) decrease in total PED volume by month 1 (P < 0.001), and this later declined further, to 0.45 mm(3), by month 9 (P = 0.0014). Total SRT volume was reduced by an average of 0.07 mm(3) at month 1 (P = 0.0159) and subsequently remained constant. CONCLUSIONS: Although neurosensory retinal edema and SRF showed an early reduction to nadir after the initiation of ranibizumab therapy, the effect on the retina was attenuated over time, suggesting possible tachyphylaxis. PED volume showed a slower but progressive reduction. Manual quantitative OCT subanalysis may allow a more precise understanding of anatomic outcomes and their correlation with visual acuity.

Joeres S, Tsong JW, Updike PG, Collins AT, Dustin L, Walsh AC, Romano PW, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #17724220 links to  free full text

Abstract: PURPOSE: To determine the intergrader reproducibility for computer-assisted grading of optical coherence tomography (OCT) images in eyes with neovascular age-related macular degeneration (AMD), by using a standardized grading procedure. METHODS: Sixty OCT image sets (of six radial lines each) were independently analyzed by two graders using validated custom software (OCTOR) to draw boundaries manually on OCT B-scans. Spaces delineated by these boundaries included retina, subretinal fluid, subretinal tissue, and pigment epithelial detachments (PEDs). Volume measurements for the nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields and the mean foveal center point (FCP) thickness were calculated by the software and compared by using weighted kappa statistics and intraclass correlation coefficients (ICCs). RESULTS: Intergrader comparison of the foveal central subfield (FCS) volume, total volume, and mean FCP thickness showed a high level of agreement and strong correlation between measurements for all spaces (kappa(weighted) = 0.72-0.97; ICC = 0.92-0.99). The best agreement was observed for total volume of the combination of all four graded spaces (kappa(weighted) = 0.97, mean difference = 0.31 mm(3), or 2.51%). The highest ICCs were seen for FCP thickness measurements. The poorest agreement was found for grading of subretinal tissue. Eyes with advanced choroidal neovascularization (CNV) and poor visibility of the retinal pigment epithelium (RPE) band appeared to show the greatest intergrader discrepancies. CONCLUSIONS: Analysis of OCT images by trained graders using computer-assisted grading software allows for highly reproducible quantitative measurements, even in eyes with complex diseases such as neovascular AMD. Quantitative subanalysis may be useful in studying the differential morphologic effect of therapies on various anatomic components.

Joeres S, Kaplowitz K, Brubaker JW, Updike PG, Collins AT, Walsh AC, Romano PW, Sadda SR. · Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA. · Ophthalmology. · Pubmed #17628685 No free full text.

Abstract: PURPOSE: To demonstrate the benefit of enhanced quantitative analysis of optical coherence tomography (OCT) images using computer-assisted grading to compare the short-term morphologic effects of pegaptanib and bevacizumab treatment for neovascular age-related macular degeneration (AMD). DESIGN: Retrospective consecutive case series. PARTICIPANTS: Fifty-three cases with neovascular AMD undergoing pegaptanib or bevacizumab therapy. METHODS: Fifty-three consecutive cases of patients who underwent StratusOCT imaging followed by treatment with either intravitreal pegaptanib (n = 18) or bevacizumab (n = 35) for neovascular AMD were retrospectively collected. Raw exported StratusOCT images were analyzed using publicly available custom software (OCTOR) designed to define the boundaries of various spaces manually. Changes in thickness and volume of the retina, subretinal fluid (SRF), subretinal tissue, and pigment epithelial detachments (PEDs) before treatment and at 3 months after treatment were calculated and compared between treatment groups. OCTOR software measurements after manual grading were also compared with the automated StratusOCT output. MAIN OUTCOME MEASURES: Volume and thickness measurements calculated by the automated StratusOCT software and the manual grading software OCTOR. RESULTS: Intravitreal bevacizumab resulted in a statistically significant greater reduction of total retinal volume than pegaptanib (-0.88+/-1.4 mm(3) vs. -0.07+/-0.5 mm(3), P = 0.003). Mean foveal central subfield (FCS) retinal volume decreased from 0.26+/-0.1 mm(3) to 0.21+/-0.1 mm(3) (P = 0.001) in the bevacizumab group and remained constant at 0.22+/-0.1 in the pegaptanib group 3 months after injection. Subanalysis of the SRF, subretinal tissue, and PEDs revealed statistically significant reductions of the total volume of all 3 spaces after bevacizumab injections but no significant change after pegaptanib treatment. Automated StratusOCT output measurements of FCS thickness, foveal center point thickness, and total volume of the retina did not reveal a statistically significant difference between the treatments. CONCLUSIONS: Differences in morphologic response between treatments were less apparent on automated StratusOCT output than on computer-assisted analysis. Although intravitreal bevacizumab was associated with a greater short-term reduction in features of exudation than pegaptanib therapy, the retrospective design of the study limits the significance of this finding. Computer-assisted subanalysis of OCT data, however, may be a useful tool in more precisely defining the anatomic effects of therapies for neovascular AMD.

Chakravarthy U, Walsh AC, Muldrew A, Updike PG, Barbour T, Sadda SR. · Doheny Retina Institute Advanced Macular Diagnostics Lab, Doheny Image Reading Center, Doheny Eye Institute, Keck School of Medicine, at the University of Southern California, Los Angeles, California 90033, USA. · Invest Ophthalmol Vis Sci. · Pubmed #17197553 links to  free full text

Abstract: PURPOSE: To compare computerized analysis with traditional grading methods in the analysis of fluorescein angiograms from patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and to examine the clinical relevance of parameters generated by computerized analysis by testing their relationships with clinical measures of vision. METHODS: Custom quantitative fluorescein analysis (QFA) software was used to analyze 62 angiograms from patients with CNV for whom distance visual acuity (DVA) data were available. On applying QFA, we obtained three mathematical parameters for each lesion component: pixel area (PA), integrated intensity (II), and positive fluorescence (PF). Quotients (Q) were derived for the latter two parameters by correcting against background (b) or optic nerve (o) fluorescence (IIQ(b), IIQ degrees , PFQ(b), and PFQ degrees ). The new metrics were compared with traditional grading parameters of classic CNV and lesion area. The relationships of both sets of angiographic data with measures of vision were explored by regression analyses. RESULTS: Weighted kappa between QFA and traditional grading for lesion subtype assessment was high (kappa = 0.7). Regression analyses with PA, IIQ(b), IIQ degrees , PFQ(b), and PFQ degrees for each lesion descriptor (leakage, classic CNV, occult CNV, total lesion) as independent variables and DVA as the dependent variable showed that in every case PFQ(b) exhibited the most significant relationship with vision (adjusted r(2) = 0.26). Parameter estimates showed that for a change of 30 units on the PFQ(b) for classic CNV, a loss of 20 letters of DVA may be expected. No parameters from traditional grading methods showed statistically significant relationships with DVA. CONCLUSIONS: The markers of dynamic change in area and intensity of fluorescence exhibited stronger relationships with visual function than did area measurements alone.

Sadda SR, Tan O, Walsh AC, Schuman JS, Varma R, Huang D. · Doheny Eye Institute, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. · Ophthalmology. · Pubmed #16647123 links to  free full text

Abstract: OBJECTIVE: To compare the detection of clinically significant diabetic macular edema (DME) by an optical coherence tomography (OCT) grid scanning protocol and biomicroscopic examination. DESIGN: Retrospective case series. PARTICIPANTS: Outpatients at the Doheny Eye Institute. METHODS: The clinical and imaging records of a consecutive series of 71 eyes of 40 patients referred for DME who underwent OCT using the both the Macular Grid 5 (MG5) scanning protocol (to allow a more evenly distributed sampling of points in the macula) and the standard Fast Macular Thickness Map (FMTM) pattern were reviewed. An automated algorithm was developed to generate a retinal thickness map using the MG5 data, which was then compared with a normative database to identify presumed areas of retinal edema. Clinically significant macular edema (CSME) was also identified by clinical examination and stereoscopic fundus photographs for comparison with the results of the OCT protocols. MAIN OUTCOME MEASURES: Sensitivity and specificity of scanning protocols. RESULTS: Optical coherence tomograms were inspected visually, and automatically detected retinal boundaries were found to be correct in 69 of 71 MG5 scans and in 65 of 71 FMTM scans. Macular Grid 5 scanning was performed twice in each eye, and the repeatability (pooled standard deviation) of the total area of edema was 0.48 mm2 (coefficient of variation, 6.8%). Sensitivity and specificity of the MG5 for detection of CSME relative to the clinical examination were 89% and 86%, respectively, with kappa being 0.74. Macular Grid 5 and FMTM assessment of foveal CSME also showed good agreement, with kappa being 0.68. CONCLUSIONS: The analysis algorithm for the OCT MG5 grid scan seems to be accurate and repeatable. Automated detection of CSME by the MG5 analysis correlated well with the clinical grading and standard OCT analysis (FMTM). Macular Grid 5 provides more information regarding the perifoveal macula than FMTM and may be of value to clinicians in planning treatment and in future studies of macular edema.

Khurana RN, Fujii GY, Walsh AC, Humayun MS, de Juan E, Sadda SR. · Doheny Retina Institute, Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. · Ophthalmology. · Pubmed #16051364 No free full text.

Abstract: OBJECTIVE: To report the recurrence of geographic atrophy (GA) in a patient with nonexudative age-related macular degeneration (AMD) after full macular translocation. DESIGN: Observational case report. METHODS: Review of the clinical, photographic, and angiographic records of a patient with GA who underwent full macular translocation. MAIN OUTCOME MEASURES: Progression of GA. RESULTS: A 73-year-old man with GA secondary to nonexudative AMD underwent a macular translocation with 360 peripheral retinectomy (MT 360) in his left eye. On postoperative month 4, fundus photography showed subtle alterations of the pigment underneath the translocated foveal region. On postoperative month 9, the visual acuity worsened to preoperative levels and there was frank retinal pigment epithelium atrophy involving the new macular region. CONCLUSIONS: The rapid recurrence and development of GA in the translocated fovea after MT 360 raise new questions regarding the pathogenesis of GA. They also raise concerns regarding the use of MT 360 in the management of nonexudative AMD.

Sadda SR, Pieramici DJ, Marsh MJ, Bressler NM, Bressler SB, Anonymous00372. · Doheny Retina Institute, Doheny Eye Institute, Los Angeles, California, USA. · Retina. · Pubmed #15579986 No free full text.

Abstract: PURPOSE: To compare the size of subfoveal lesions based on photographic documentation before and after submacular surgery of choroidal neovascularization (CNV) lesions. METHODS: Subfoveal lesion sizes at baseline and month 3 follow-up visits for patients assigned to surgery in the Submacular Surgery Trials (SST) Pilot Study were assessed categorically using Macular Photocoagulation Study (MPS) disc area (DA) circles. The Submacular Surgery Trials Pilot Study groups reviewed were as follows: Group N (age-related macular degeneration [AMD]; lesion <50% blood; classic CNV present; size < or =9 MPS DAs); Group R (AMD; prior nonfoveal laser; classic CNV present; size < or =9 MPS DAs); Group B (AMD; lesion > or =50% blood); and Group H (ocular histoplasmosis syndrome or idiopathic; classic CNV present; size < or =9 MPS DAs). RESULTS: Postoperative month 3 lesion size was at least 1 size category smaller than the preoperative lesion size in 6% (4/66) of Group N, 0 (0/31) of Group R, 6% (2/34) of Group H, and 45% (18/40) of Group B eyes. In Group H eyes, there was no size change in 50% (17/34), and enlargement was found in 44% (15/34). For eyes in Groups N and R, approximately one third remained stable (20/66, 30% and 12/31, 39%, respectively), whereas two thirds enlarged by at least 1 category (42/66, 64% and 19/31, 61%, respectively). CONCLUSIONS: The change in lesion size after submacular surgery was variable, with a tendency for Group H lesions to remain the same size or larger, Group B lesions to measure smaller, and Group N and Group R lesions to be larger.

del Cerro M, Humayun MS, Sadda SR, Cao J, Hayashi N, Green WR, del Cerro C, de Juan E. · Department of Ophthalmology, University of Rochester School of Medicine, New York, USA. · Invest Ophthalmol Vis Sci. · Pubmed #10967076 links to  free full text

Abstract: PURPOSE: To describe the histologic findings of the transplanted eye of a 94-year-old man with neovascular age-related macular degeneration, who 3 years earlier underwent subretinal transplantation of both a fetal neural retinal sheet and a retinal microaggregrate suspension. METHODS: Serial sections of the posterior segment of the eye and the transplanted areas were processed and studied by routine histologic techniques, including both light and transmission electron microscopy (TEM). Transplanted areas were also examined for the presence of glial, neuronal, and photoreceptor cell markers by standard immunohistochemical methods. RESULTS: After transplantation in this patient, there was no visual improvement. Light microscopic examination disclosed survival of the transplanted cells in the subretinal space with no evidence of inflammation or rejection. The neural retinal sheet transplant developed a layered configuration. The retinal pigment epithelium (RPE) was absent over much of the posterior pole, including the area of transplantation. TEM examination and immunohistochemical analysis disclosed the presence of neuronal and glial cells within the transplant. A few transplant neuronal cell processes overlying a focus of residual RPE cells were positive for S-antigen, but well-developed photoreceptor outer segments were not present. CONCLUSIONS: Long-term survival of transplanted neural retinal tissue can be achieved in human patients without immunosuppression. The lack of photoreceptor development in this patient may be the result of absent or dysfunctional RPE. Nonetheless, the long-term survival of grafted tissue in the human subretinal space in the absence of immunosuppressive treatment is promising for future efforts in the field of neural retinal transplantation.

Keane PA, Liakopoulos S, Walsh AC, Sadda SR. · No affiliation provided · Br J Ophthalmol. · Pubmed #19174407 No free full text.

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