Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Surgical Observations From the First 120 Cases of Subretinal Gene Therapy for Inherited Retinal Diseases.

PURPOSE: To report surgical observations formulated during the first 120 cases of subretinal gene therapy in patients with inherited retinal degenerations (IRDs). METHODS: A two-surgeon team compiled surgical observations and formulated surgical pearls based on the consecutive cases of subretinal viral vector injection in patients enrolled in clinical trials focusing on choroideremia, achromatopsia, and RP GTPase regulator associated retinitis pigmentosa, as well as patients with retinal pigment epithelium-specific-65-kDa (RPE65) associated Leber congenital amaurosis receiving Food and Drug Administration-approved voretigene neparvovec-rzyl therapy. RESULTS: One hundred twenty subretinal surgeries were performed by a two-surgeon team. Key anatomical features pertinent to surgical management were noted and are described in this article. Surgical decision making for successful subretinal administration of viral vectors and management of potential surgical challenges were formulated. CONCLUSION: Lessons learned during subretinal gene therapy cases may be helpful to other surgeons entering clinical trials or performing postapproval gene therapy administration. Surgical pearls outlined in this article may also be helpful for other targeted subretinal therapies, such as cellular transplantation or retinal prosthesis implantation.

Autologous Retinal Transplantation for Primary and Refractory Macular Holes and Macular Hole Retinal Detachments: The Global Consortium.

PURPOSE: To report the anatomic and functional outcomes of autologous retinal transplantation (ART). DESIGN: Multicenter, retrospective, interventional, consecutive case series. PARTICIPANTS: One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. METHODS: All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. MAIN OUTCOME MEASURES: Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. RESULTS: One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P < 0.001) after surgery (mean follow-up, 8.6 ± 0.8 months). Autologous retinal transplantation was performed for primary MH repair in 27% of patients (n = 35), for refractory MH in 58% of patients (n = 76; mean number of previous surgeries, 1.6 ± 0.2), and for MH-RRD in 15% of patients (n = 19). Mean maximum MH diameter was 1470 ± 160 µm, mean minimum diameter was 840 ± 94 µm, and mean axial length was 24.6 ± 3.2 mm. Overall, 89% of MHs closed (78.5% complete; 10% small eccentric defect), with a 95% closure rate in MH-RRD (68.4% complete; 26.3% small eccentric defect). Visual acuity improved by at least 3 lines in 43% of eyes and by at least 5 lines in 29% of eyes. Reconstitution of the EZ (P = 0.02) and ANL (P = 0.01) on OCT were associated with better final VA. Five cases of ART graft dislocation (3.8%), 5 cases of postoperative retinal detachment (3.8%), and 1 case of endophthalmitis (0.77%) occurred. CONCLUSIONS: In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies.

BACKGROUND: Since they were first derived more than three decades ago, embryonic stem cells have been proposed as a source of replacement cells in regenerative medicine, but their plasticity and unlimited capacity for self-renewal raises concerns about their safety, including tumour formation ability, potential immune rejection, and the risk of differentiating into unwanted cell types. We report the medium-term to long-term safety of cells derived from human embryonic stem cells (hESC) transplanted into patients. METHODS: In the USA, two prospective phase 1/2 studies were done to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt's macular dystrophy (age >18 years) and nine with atrophic age-related macular degeneration (age >55 years). Three dose cohorts (50,000, 100,000, and 150,000 cells) were treated for each eye disorder. Transplanted patients were followed up for a median of 22 months by use of serial systemic, ophthalmic, and imaging examinations. The studies are registered with ClinicalTrials.gov, numbers NCT01345006 (Stargardt's macular dystrophy) and NCT01344993 (age-related macular degeneration). FINDINGS: There was no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events were associated with vitreoretinal surgery and immunosuppression. 13 (72%) of 18 patients had patches of increasing subretinal pigmentation consistent with transplanted retinal pigment epithelium. Best-corrected visual acuity, monitored as part of the safety protocol, improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, whereas the untreated fellow eyes did not show similar improvements in visual acuity. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16-25 points 3-12 months after transplantation in patients with atrophic age-related macular degeneration and 8-20 points in patients with Stargardt's macular dystrophy. INTERPRETATION: The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease. Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement. FUNDING: Advanced Cell Technology.

REPRODUCIBILITY AND COMPARISON OF VISUAL ACUITY OBTAINED WITH SIGHTBOOK MOBILE APPLICATION TO NEAR CARD AND SNELLEN CHART.

PURPOSE: To investigate test-retest reproducibility of visual acuities obtained with a popular mobile application (app) and to explore the agreement with the standard clinic charts. METHODS: Records of patients who had visual acuity measured during the same routine clinic visit with Snellen chart, Rosenbaum near vision card, and SightBook mobile app were reviewed. Acuities were converted to approximate ETDRS letters for statistical purposes. RESULTS: One hundred and twenty-six patients were identified. SightBook, Snellen, and near card acuities had excellent test-retest reproducibility. SightBook acuities were significantly different from the near card acuities (mean absolute difference of 5.4 and 6.1 letters in the right and left eyes) and the Snellen acuities (mean absolute difference of 7.7 and 7.9 letters in the right and left eyes). The agreement was also poor between the near card and the Snellen acuities (mean absolute difference of 6.4 and 7.6 letters in the right and left eyes). CONCLUSION: The discrepancy between SightBook mobile app and the clinic charts acuities may be large; however, the results are highly reproducible. Obtaining baseline SightBook acuity allows future vision comparisons. SightBook mobile app offers a new portable vision assessment tool for the office and remote patient monitoring.

Worldwide Argus II implantation: recommendations to optimize patient outcomes.

BACKGROUND: A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. METHODS: Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. RESULTS: Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. CONCLUSIONS: Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

Visual and anatomical outcomes of macular epiretinal membrane peeling after previous rhegmatogenous retinal detachment repair.

PURPOSE: To report outcomes and prognostic factors after epiretinal membrane peeling in patients with previous rhegmatogenous retinal detachment repair. METHODS: A consecutive case series. Best-corrected visual acuity and optical coherence tomography characteristics were analyzed before and after epiretinal membrane surgery. RESULTS: Fifty-three eyes were analyzed. Best-corrected visual acuity improved by a mean of 10 letters at 1 month (N = 45; P = 0.001), 15 at 3 months (N = 42; P < 0.001), 11 at 6 months (N = 35; P = 0.001), and 16 at 12 months (N = 33; P < 0.001). The mean optical coherence tomography central foveal thickness decreased by 141 (N = 22; P < 0.001), 185 (N = 24; P < 0.001), 180 (N = 17; P = 0.001), and 151 µm (N = 9; P = 0.017) at 1, 3, 6, and 12 months, respectively. Better preoperative best-corrected visual acuity correlated with better best-corrected visual acuity at all follow-up visits (P ≤ 0.001). Intact preoperative inner segment/outer segment junction and external limiting membrane line, but not the change in central foveal thickness or location of fluid, correlated with better postoperative best-corrected visual acuity through 6 months. CONCLUSION: Epiretinal membrane peeling after previous rhegmatogenous retinal detachment repair resulted in significant improvements in visual acuity and optical coherence tomography thickness, even in eyes with previous macula-involving rhegmatogenous retinal detachment. Better preoperative visual acuity and intact outer retinal layers by optical coherence tomography were the main prognostic factors for visual outcomes.

Self-Inflicted Laser-Induced Retinopathy.

This photo essay details a patient with self-inflicted laser-induced retinal injury progressing to full-thickness macular holes in both eyes. A 40-year-old patient presented after a self-inflicted injury by a handheld class 3 blue laser (450 nm) he purchased on the internet. The patient reported shining the laser through a window, which reflected the beam back into his eyes. Visual acuity was measured at 20/400 in both eyes. The initial fundus photographs revealed vitreous and preretinal hemorrhages in the right eye, and multiple yellow-white fresh laser burns in the macula of the left eye. Optical coherence tomography (OCT) showed preretinal hemorrhage in the right eye and retinal disruption with preretinal hyper-reflective lesion in the left eye. After one month, his vision deteriorated to finger counting in each eye. He developed a full-thickness macular hole and hyperfluorescent curvilinear streaks in the superior maculae in both eyes. OCT images showed retinal pigment epithelium clumping and outer retinal atrophy in curvilinear streak areas in both eyes, which point to self-inflicted injury. This case illustrates laser-pointer-induced retinopathy and reinforces the necessity of public education on the dangers of utilizing handheld lasers without eye protection.

Wide-field spectral-domain optical coherence tomography in patients and carriers of X-linked retinoschisis.

PURPOSE: To evaluate macular and extramacular retinal anatomy in patients and carriers of X-linked retinoschisis (XLRS) using a wide-field spectral-domain optical coherence tomography (SD-OCT) imaging technique. DESIGN: Case series. PARTICIPANTS: Six XLRS-affected male subjects and 3 XLRS female carriers. METHODS: The subjects prospectively underwent XLRS DNA genotyping and comprehensive ophthalmic examination, including visual acuity, 30-2 Humphrey visual field, fundus photography, and wide-field SD-OCT, a montage technique to generate SD-OCT images spanning approximately 50 degrees horizontally and 35 degrees vertically of the posterior pole. MAIN OUTCOME MEASURES: Distribution and location of schisis cavities. RESULTS: Among male subjects affected by XLRS, asymmetric bilateral schisis was seen in all eyes imaged with montage SD-OCT (11 eyes). Wide-field OCT images demonstrated schisis cavities only in the central macula in 6 eyes (55%), throughout the macula extending to the outside of the temporal arcades in 3 eyes (27%), and throughout the macula extending nasal to the optic nerve in 2 eyes (18%). Cystoid spaces accounting for macular splitting were present in the inner nuclear layer (INL) in all 11 eyes and in the outer nuclear layer (ONL) in 4 eyes. A few small cysts were seen parafoveally in the ganglion cell layer (GCL) or nerve fiber layer (NFL) in 4 eyes. Subclinical extramacular schisis spaces were seen (n=5 eyes) within the INL in 1 eye, the ONL in 1 eye, the INL/GCL/NFL in 1 eye, the ONL/GCL/NFL in 1 eye, and the INL/ONL/GCL/NFL in 1 eye. Schisis was rarely seen nasal to the optic nerve (2 eyes). Central/paracentral visual field defects were seen in 9 eyes. Female carriers did not show schisis on examination or OCT. CONCLUSIONS: Wide-field SD-OCT is a useful tool for evaluating complex retinal anatomy. In patients with XLRS, the foveomacular schisis was seen most frequently in the INL. Subclinical extramacular schisis was seen in 45% of eyes and was equally prevalent in the INL, ONL, and GCL/FNL. The GCL/FNL cystoid spaces were small and seen near the fovea and the arcades only. Carriers were schisis-free. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Needle aspiration for management of acute intraoperative fluid misdirection during phacoemulsification.

Purpose: Acute intraoperative fluid misdirection is a serious complication that may occur during phacoemulsification. We provide a detailed description and a video of our preferred technique for prompt management of acute intraoperative fluid misdirection. Observations: A 79-year-old male developed sudden shallowing of the anterior chamber and marked elevation of intraocular pressure at hydrodissection during phacoemulsification surgery. Treatment consisted of a needle aspiration of trapped fluid from the retrolental space, employing a 5/8th inch, 25-gauge needle on a medium-size syringe leading to immediate softening of the globe and deepening of the anterior chamber. The rest of the case proceeded uneventfully. The patient had uncomplicated recovery and final best-corrected visual acuity of 20/20. Conclusions and importance: Acute subcapsular infusion fluid entrapment may occur during uneventful phacoemulsification. Needle aspiration of retrolental fluid is a simple and inexpensive method for immediate resolution of high IOP and deepening of the anterior chamber, allowing the case to proceed.

Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease.

Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or middle adulthood and causes progressive, irreversible visual impairment and blindness. No effective treatment is currently available. In the present article, we review the most recent updates in clinical trials targeting the management of STGD1, including gene therapy, small molecule therapy, and stem cell therapy. In gene therapy, dual adeno-associated virus and non-viral vectors have been successful in delivering the human ABCA4 gene in preclinical studies. For pharmaceutical therapies ALK-001, deuterated vitamin A shows promise with preliminary data for phase 2 trial, demonstrating a decreased atrophy growth rate after two years. Stem cell therapy using human pluripotent stem cell-derived retinal pigment epithelium cells demonstrated long-term safety three years after implantation and visual acuity improvements in the first two years after initiation of therapy. Many other treatment options have ongoing investigations and clinical trials. While multiple potential interventions have shown promise in attenuating disease progression, further exploration is necessary to demonstrate treatment safety and efficacy.

Current Assistive Devices Usage and Recommendations for a Future Artificial Vision Prosthesis among Patients with Severe Visual Impairment Due to Inherited Retinal Diseases.

Patients with inherited retinal diseases (IRDs) utilize various adaptive techniques and devices designed to assist them with activities of daily living (ADLs). The purpose of this study was to assess the assistive devices used by patients with IRDs, the difficulties they face despite these devices, and their recommendations for a future visual prosthesis. In collaboration with blind patients, an online survey was developed and administered to adults with IRDs and visual acuities of 20/400 to no light perception in the better-seeing eye. We analyzed data from 121 survey respondents (aged 18 to >80 years). Five respondents were Argus II prosthesis recipients. The most commonly used aids were cellular phones/tablets for reading (63.6%) as well as a sighted guide (75.0%) and a cane (71.4%) for mobility. Despite current assistive devices, participants reported continued difficulty with ADLs. Improved navigation, reading, and facial recognition were ranked the most desirable features for future visual prostheses. Argus II recipients suggested technology with improved ability to recognize objects and obstacles, detect movement, and cut out busy backgrounds. These insights are valuable in shaping the design of future prosthetic devices tailored to the needs of IRD patients.

Bilateral exudative retinal detachments after subretinal gene therapy with voretigene neparvovec-rzyl for RPE65 Leber Congenital Amaurosis.

Purpose: To report panuveitis with exudative retinal detachments in a healthy 27-year-old woman with biallelic mutations in the RPE65 gene, who underwent bilateral sequential gene therapy with subretinal administration of voretigene neparvovec-rzyl. Observations: Visual acuity improved for 30 days after surgery as oral corticosteroids were tapered. At postoperative week 6, vision declined due to sudden onset uveitis and exudative retinal detachments in both eyes. HLA Class II typing revealed the haplotype associated with sympathetic ophthalmia and Vogt-Koyanagi-Harada (VKH). The inflammation improved after corticosteroid, mycophenolate mofetil, and adalimumab therapy while vision remained poor. Conclusions and Importance: Surgically-induced sympathetic ophthalmia is a plausible explanation for the clinical findings; surgery of both eyes within one week would conceal the inciting eye. VKH or inflammation related to the gene therapy are other possible etiologies but severe bilateral panuveitis has not been reported with voretigene neparvovec-rzyl. Informed consent for gene therapy surgery should include a discussion of the rare complication of sympathetic ophthalmia following vitrectomy surgery.

Visual Acuity, Retinal Morphology, and Patients' Perceptions after Voretigene Neparovec-rzyl Therapy for RPE65-Associated Retinal Disease.

OBJECTIVE: To explore the effect of patients' age, baseline visual acuity (VA), and intraoperative foveal detachment on outcomes of subretinal voretigene neparvovec-rzyl (Luxturna) therapy and to assess patients' perceptions of the treatment effect. DESIGN: Multicenter, retrospective, consecutive case series, and cross-sectional prospective survey. PARTICIPANTS: All 41 consecutive patients treated with voretigene neparvovec-rzyl after Food and Drug Administration approval at 3 institutions between January 2018 and May 2020. METHODS: A retrospective chart review of operative reports, clinical notes, ancillary testing, and complications, comparing data at baseline and at 1, 2 to 3, 6 to 9, and 10 to 15 months after subretinal surgery was conducted. A survey was administered to adult patients and parents of pediatric patients. MAIN OUTCOME MEASURES: Changes in best-corrected VA and retinal morphology and in patients' perceptions. RESULTS: Seventy-seven eyes of 41 patients (16 adults and 25 pediatric patients; age range, 2-44 years; mean follow-up, 10 months [range, 1 week to 18.5 months]) were analyzed. There was no statistically significant vision change for the adults, whereas there was a trend of improvement for pediatric patients, which reached statistical significance for some time points. The baseline VA did not affect the posttherapy VA (P = 0.23). The central foveal thickness decreased mildly in both pediatric patients and adults, without significant differences between the populations. The fovea was detached by voretigene neparvovec-rzyl in 62 (81%) eyes. The inner segment-outer segment junction remained unchanged in 91% of 54 eyes with gradable OCT, with or without foveal detachment. Thirty-two (78%) patients were reached for the survey an average of 1.15 ± 0.50 years (range, 0.31 to 2.31) after the surgery in the first eye. Improvement in night, day, or color vision was reported by 23 (72%), 22 (69%), and 18 (56%) patients, respectively. CONCLUSIONS: This study is limited by the large variability in follow-up time. There were no persistent statistically significant vision changes. A decrease in foveal thickness was noted in most eyes, but the long-term significance of this remains to be determined.

Spectral domain optical coherence tomography imaging of drusen in nonexudative age-related macular degeneration.

PURPOSE: To measure drusen area and volume in eyes with nonexudative age-related macular degeneration (AMD) using spectral domain optical coherence tomography imaging (SD-OCT). DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: One hundred three eyes from 74 patients with drusen. METHODS: Patients with drusen secondary to nonexudative AMD were enrolled in this study. Five separate SD-OCT scans, each consisting of 40 000 uniformly spaced A-scans organized as 200 A-scans in each B-scan and 200 horizontal B-scans, were performed on each eye. Each scan covered a retinal area of 6×6 mm centered on the fovea. A novel algorithm was used to quantitatively assess drusen area and volume. Measurements from the entire scans, as well as in regions contained within 3- and 5-mm circles centered on the fovea, were analyzed. Test-retest standard deviations of drusen area and volume measurements were calculated for each eye. MAIN OUTCOME MEASURES: Drusen area and volume. RESULTS: The algorithm created drusen maps that permitted both qualitative and quantitative assessment of drusen area and volume. Both the qualitative appearance and the quantitative measurements of drusen area and volume were highly reproducible over the 5 different datasets. The intraclass correlation coefficient was >0.99 for both area and volume measurements on the entire dataset as well as the 3- and 5-mm circles. The correlation between lesion size and the test-retest standard deviations can be eliminated by performing a square root transformation of the area measurements and a cube root transformation of the volume measurements. These transformed data allowed for the inclusion of all drusen sizes in the calculation of an estimated single pooled test-retest standard deviation, which will be useful for longitudinal studies of drusen natural history. CONCLUSIONS: A novel algorithm for the qualitative and quantitative assessment of drusen imaged using SD-OCT was shown to be highly reproducible. The ability to assess drusen volume reliably represents a new quantitative parameter to measure in AMD and may be useful when assessing disease progression, particularly in trials for treatments of nonexudative AMD.