Historical Perspectives on the Management of Macular Degeneration, Diabetic Retinopathy, and Retinal Detachment: Personal Reminiscences.

We were challenged and delighted when Dr. Sharon Solomon, guest editor of this Retina Supplement, invited us to reminisce about caring for patients with common retinal disorders before there was access to the diagnostic and therapeutic tools that are readily available today. We agreed to confine our remarks to 3 common, but serious, conditions: age-related macular degeneration (Dr. Fine), diabetic retinopathy (Dr. Goldberg), and retinal detachment (Dr. Tasman). Each of us completed our ophthalmology training about half a century ago. At that time, a patient who received any 1 of the 3 diagnoses was at considerable risk of severe and irreversible loss of vision. Most readers today will have little if any experience in evaluating and treating such patients without access to a plethora of diagnostic and therapeutic technologies, including intravenous fluorescein angiography, laser photocoagulation, optical coherence tomography, ophthalmic ultrasound, angioinhibitory drugs, vitrectomy, intraocular gases, and many others. We are both pleased and privileged that each of us has practiced our profession long enough to enjoy what the enormous technological developments of the past half century, as described in this article, have meant for our patients.

The Evolution of the American Board of Ophthalmology Written Qualifying Examination.

Since the inception of board certification in ophthalmology in 1916, a written assessment of candidates' knowledge base has been an integral part of the certification process. Although the committee structure and technique for writing examination questions has evolved over the past 100 years, the written qualifying examination remains an essential tool for assessing the competency of physicians entering the workforce. To develop a fair and valid examination, the American Board of Ophthalmology builds examination questions using evidence-based, peer-reviewed literature and adheres to accepted psychometric assessment standards.

Low vision depression prevention trial in age-related macular degeneration: a randomized clinical trial.

PURPOSE: To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). DESIGN: Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. PARTICIPANTS: Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). INTERVENTIONS: Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. MAIN OUTCOME MEASURES: The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). RESULTS: At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. CONCLUSIONS: An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry, rehabilitation, psychiatry, and behavioral psychology may prevent depression in this population.

Personal reminiscences of ophthalmology giants of the 20th century.

This paper records personal reminiscences of seven 20th century ophthalmologists who each in his own way metaphorically split the atom and, thereby, changed ophthalmology forever. In addition to their major contributions, they each shared some very desirable traits. They were gentlemen who were devoted to their families and their families to them.

Improving function in age-related macular degeneration: a randomized clinical trial.

PURPOSE: To compare the efficacy of problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD). DESIGN: Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). PARTICIPANTS: Patients with AMD (n = 241) attending retina practices. INTERVENTIONS: Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment. MAIN OUTCOME MEASURES: We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life (QoL). RESULTS: There were no between-group differences in TVF scores at 3 (P = 0.47) or 6 (P = 0.62) months. For PST subjects, mean ± standard deviation TVF scores improved from 2.71±0.52 at baseline to 2.18±0.88 at 3 months (P = 0.001) and were 2.18±0.95 at 6 months (change from 3 to 6 months, P = 0.74). For ST subjects, TVF scores improved from 2.73±0.52 at baseline to 2.14±0.96 at 3 months (P = 0.001) and were 2.15±0.96 at 6 months (change from 3 to 6 months, P = 0.85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs 78.6%, respectively; P = 0.83) and 6 months (76.2% vs 79.1%, respectively; P = 0.61). There were no changes in the NEI VFQ or AI. Vision-related QoL improved for PST relative to ST subjects at 3 months (F(4, 192) = 2.46; P = 0.05) and at 6 months (F(4, 178) = 2.55; P = 0.05). The PST subjects also developed more adaptive coping strategies than ST subjects. CONCLUSIONS: We found that PST was not superior to ST at improving vision function in patients with AMD, but that PST improved their vision-related QoL. Despite the benefits of anti-vascular endothelial growth factor treatments, AMD remains associated with disability, depression, and diminished QoL. This clinical reality necessitates new rehabilitative interventions to improve the vision function and QoL of older persons with AMD. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Retinopathy of prematurity: do we still have a problem?: the Charles L. Schepens lecture.

OBJECTIVE: To assess the present-day prevalence of retinopathy of prematurity (ROP) worldwide. METHODS: A search of the literature was conducted to better define the worldwide experience with ROP. An interview was also conducted with 2 schools for the blind, Overbrook in Philadelphia, Pennsylvania, and Perkins in Watertown, Massachusetts. The study also is based on personal experience with ROP over the last 49 years. RESULTS: Worldwide, the prevalence of ROP is on the rise in developing countries, and some of those ROP-affected premature infants are heavier than 1500 g. In western countries, extremely low-birth-weight infants (≤1000 g) are also surviving. Currently, the Overbrook School for the Blind has 11 of 55 children between the ages of 3 and 5 years with ROP (20%). The Perkins School has 34 of 200 children from birth to age 3 years with ROP (17%). During 2009, 47 babies had laser treatment for ROP in the neonatal intensive care unit of Jefferson Medical College by physicians from Wills Eye Hospital. Twenty-four infants had been identified in a screening of 591 patients (4.1%). The other 23 had been referred in for treatment. In 2009, we had 187 outpatient visits related to ROP ranging from 6 months to 67 years of age. CONCLUSIONS: Because more and more extreme low-birth-weight infants are surviving in western countries and because of the rising numbers of surviving premature infants in emerging nations, we may be on the verge of an ROP epidemic.

Psychological and cognitive determinants of vision function in age-related macular degeneration.

OBJECTIVE: To investigate the effect of coping strategies, depression, physical health, and cognition on National Eye Institute Visual Function Questionnaire scores obtained at baseline in a sample of older patients with age-related macular degeneration (AMD) enrolled in the Improving Function in AMD Trial, a randomized controlled clinical trial that compares the efficacy of problem-solving therapy with that of supportive therapy to improve vision function in patients with AMD. METHODS: Baseline evaluation of 241 older outpatients with advanced AMD who were enrolled in a clinical trial testing the efficacy of a behavioral intervention to improve vision function. Vision function was characterized as an interval-scaled, latent variable of visual ability based on the near-vision subscale of the National Eye Institute Vision Function Questionnaire-25 plus Supplement. RESULTS: Visual ability was highly correlated with visual acuity. However, a multivariate model revealed that patient coping strategies and cognitive function contributed to their ability to perform near-vision activities independent of visual acuity. CONCLUSIONS: Patients with AMD vary in their coping strategies and cognitive function and in their visual acuity, and that variability determines patients' self-report of vision function. Understanding patient coping mechanisms and cognition may help increase the precision of vision rating scales and suggest new interventions to improve vision function and quality of life in patients with AMD. Trial Registration  clinicaltrials.gov Identifier: NCT00572039.

Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

Optical coherence tomography imaging of the fovea in retinopathy of prematurity.

BACKGROUND AND OBJECTIVE: To report foveal optical coherence tomography (OCT) findings in patients with a history of retinopathy of prematurity (ROP). PATIENTS AND METHODS: In a case-control study, OCT imaging of the fovea was performed on mostly adult patients with a history of ROP and no significant macular pathology. The same OCT imaging was performed on control subjects who were born full-term. RESULTS: Fourteen eyes of 12 patients with ROP were studied. Mean age was 39 years and mean gestational age at birth was 28 weeks. Of the 11 eyes with no cataract or pseudophakia, median best-corrected visual acuity was 20/40. Three eyes with cataracts had visual acuities of 20/50, 20/60, and 20/100. OCT imaging showed that eyes in the ROP group had a relative loss of the foveal depression, increased macular thickness, and continuation of inner retinal layers within the fovea. CONCLUSION: OCT imaging demonstrated abnormal foveal architecture in patients with a history of ROP, but most of these patients maintained good visual acuity.

Activity loss is associated with cognitive decline in age-related macular degeneration.

BACKGROUND/METHODS: The objective of this study was to determine whether relinquishing cognitive, physical, and social activities is associated with an increased risk of cognitive decline in patients with age-related macular degeneration (AMD). We conducted a 3-year longitudinal study of 206 nondemented patients with AMD. RESULTS: Twenty-three subjects (14.4%) declined cognitively. Age, sex, education, decline in visual acuity, and number of dropped activities were associated with cognitive decline; each additional dropped activity increased the risk by 58%. Subjects who relinquished three activities were 3.87 times (95% confidence interval, 1.95-7.76) more likely to become demented than subjects who relinquished no activities; those who relinquished five activities were 9.54 times (95% confidence interval, 3.05-30.43) more likely. A multivariate model demonstrated that number of dropped activities was a powerful predictor of cognitive decline after controlling for relevant risk factors, particularly for subjects younger than 80 years of age. CONCLUSIONS: Relinquishing valued activities is associated with an increased risk of cognitive decline in older patients with vision loss caused by AMD. These data suggest the importance of promoting optimal cognitive and physical health in patients with AMD and perhaps other chronic diseases.

Combination intravitreal bevacizumab/panretinal photocoagulation versus panretinal photocoagulation alone in the treatment of neovascular glaucoma.

PURPOSE: To evaluate same-day combination intravitreal bevacizumab/panretinal photocoagulation (PRP) for the treatment of neovascular glaucoma (NVG) compared with PRP alone. METHODS: This was an institutional review board-approved, retrospective, consecutive case-control study of patients receiving same-day combination bevacizumab/PRP or PRP alone as treatment of NVG from September 2004 through June 2007. Visual acuity, intraocular pressure (IOP), presence of anterior segment neovascularization, and required glaucoma interventional procedures were recorded. RESULTS: A total of 23 patients were identified, 11 in the bevacizumab/PRP group and 12 in the PRP alone group. The bevacizumab/PRP group had a significant reduction in IOP compared with the PRP alone group (-11 vs. 0 mmHg, respectively; P = 0.03). There was a significantly higher frequency and rate of neovascular regression in the combination therapy group than in the PRP only group (11 vs 2 eyes [P < 0.001] and 12 vs 127 days [P < 0.0001], respectively). Average follow-up was 143 days for the bevacizumab/PRP group and 118 days for the PRP alone group. CONCLUSIONS: Combination treatment resulted in more rapid decrease in IOP. In addition, the combination group had increased frequency and rapidity of regression of neovascularization. This study provides a foundation for further research and suggests consideration for a possible new paradigm for the treatment of NVG.

Myopia in adults with retinopathy of prematurity.

PURPOSE: To evaluate myopia in adults with retinopathy of prematurity (ROP). DESIGN: Observational case series. METHODS: Axial length (AL), corneal radius (CR), and AL/CR ratio were measured in myopic adults with ROP using ultrasound A-scan biometry and keratometry, respectively. RESULTS: Twenty-five eyes of 18 patients (mean age, 48 years) were studied. Mean gestational age at birth was 29 weeks. The average refraction was -5.23 diopters, AL 24.43 mm, CR 7.45 mm, and AL/CR ratio 3.28. On average, myopic adults with ROP had a shorter AL and decreased CR (increased corneal curvature), but a similar AL/CR ratio, relative to adults with the same degree of myopia who were born full-term. Myopic adults with ROP also had increased lens thickness (LT) and shallow anterior chamber depth (ACD). CONCLUSIONS: Myopic adults with ROP had a shorter AL and smaller CR than expected for their degree of myopia. However, AL/CR ratios for these patients were similar to the values of adults who were born full-term. These results suggest that the refractive element most responsible for myopia in adults with ROP is higher corneal curvature (decreased CR), whereas the predominant factor in adult myopic individuals who were born full-term is increased AL. We believe that increased LT and shallow ACD make a lesser contribution to myopia in adults with ROP.

Adult retinopathy of prematurity: retinal complications from cataract surgery.

PURPOSE: To describe the results and retinal complications of cataract surgery in adults with a history of premature birth from two separate retina services. DESIGN: Retrospective, noncomparative, interventional, consecutive case series. METHODS: A retrospective chart review was carried out of two cohorts of patients: Beaumont Hospital and Wills Eye Institute. Eyes of patients were selected who had a birth weight of less than 2200 g or a gestational age of fewer than 32 weeks, were 15 years of age or older at baseline visit, and who underwent cataract surgery in one or both eyes with at least one follow-up examination. A total of 66 eyes from 45 patients were selected and subject to analysis. RESULTS: Thirty-seven eyes (56%) had minimal cicatricial changes resulting from Retinopathy of Prematurity (ROP). The mean age of cataract surgery was 40.3 years. Twenty-five eyes (38%) had at least a one-line improvement in vision, 20 eyes (30%) had no change in vision, and 21 eyes (32%) had a decline in vision after cataract surgery. A postoperative complication of a retinal tear or retinal detachment developed in 15 (23%) of 66 eyes. The severity of the baseline fundus changes resulting from ROP did not correlate with the likelihood of developing a postcataract surgery complication. Results were similar between the two cohorts. CONCLUSIONS: In patients with a history of premature birth, cataract surgery tends to be performed at a young age, has a mixed range of visual results, and can be associated with a high rate of retinal complications.

Preventing depression in age-related macular degeneration.

CONTEXT: Age-related macular degeneration is a prevalent disease of aging that may cause irreversible vision loss, disability, and depression. The latter is rarely recognized or treated in ophthalmologic settings. OBJECTIVE: To determine whether problem-solving treatment can prevent depressive disorders in patients with recent vision loss. DESIGN: Randomized, controlled trial. SETTING: Outpatient ophthalmology offices in Philadelphia, Pennsylvania. PATIENTS: Two hundred six patients aged 65 years or older with recent diagnoses of neovascular age-related macular degeneration in one eye and pre-existing age-related macular degeneration in the fellow eye. INTERVENTION: Patients were randomly assigned to problem-solving treatment (n = 105) or usual care (n = 101). Problem-solving treatment therapists delivered 6 sessions during 8 weeks in subjects' homes. MAIN OUTCOME MEASURES: Outcomes were assessed at 2 months for short-term effects and 6 months for maintenance effects. These included DSM-IV-defined diagnoses of depressive disorders, National Eye Institute Vision Function Questionnaire-17 scores, and rates of relinquishing valued activities. RESULTS: The 2-month incidence rate of depressive disorders in problem-solving-treated subjects was significantly lower than controls (11.6% vs 23.2%, respectively; odds ratio, 0.39; 95% confidence interval, 0.17-0.92; P = .03). Problem-solving treatment also reduced the odds of relinquishing a valued activity (odds ratio, 0.48; 95% confidence interval, 0.25-0.96; P = .04). This effect mediated the relationship between treatment group and depression. By 6 months, most earlier observed benefits had diminished, though problem-solving treatment subjects were less likely to suffer persistent depression (chi2(1,3) = 8.46; P = .04). CONCLUSIONS: Problem-solving treatment prevented depressive disorders and loss of valued activities in patients with age-related macular degeneration as a short-term treatment, but these benefits were not maintained over time. Booster or rescue treatments may be necessary to sustain problem-solving treatment's preventative effect. This study adds important new information to the emerging field of enhanced-care models to prevent or treat depression in older persons. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00042211.

Dissatisfaction with performance of valued activities predicts depression in age-related macular degeneration.

OBJECTIVE: To determine whether dissatisfaction with performance of valued activities predicts depression in patients with age-related macular degeneration (AMD). PATIENTS: Two hundred and six patients with newly diagnosed neovascular AMD in one eye and pre-existing AMD in the fellow eye who were participating in a clinical trial of a psychosocial intervention to prevent depression. MEASURES: Structured clinical evaluations of vision function, depression, visual acuity, contrast sensitivity and medical morbidity. Subjects were classified as dissatisfied if they indicated that they were dissatisfied with their performance of a valued activity. RESULTS: Subjects who were dissatisfied with performance of valued activities (n = 71) had similar demographic characteristics to satisfied subjects (n = 135) but had worse visual acuity (p < 0.054), greater medical comorbidity (p < 0.006), and lower vision function (p < 0.001). Dissatisfied subjects were almost 2.5 times more likely (OR = 2.41; [95% CI 1.02, 5.65]; p = 0.044) to become depressed within 2 months than satisfied subjects independent of baseline visual acuity, vision function, and medical comorbidity. CONCLUSION: Dissatisfaction with performance of valued activities in older persons with AMD predicts depression over a 2-month period. Assessing the ability to pursue valued activities may identify patients at risk for depression and prompt clinicians to initiate rehabilitative interventions and careful surveillance for depression.

Laser treatment for retinopathy of prematurity: evolution in treatment technique over 15 years.

PURPOSE: To assess the number of laser burns applied to the peripheral retina to treat retinopathy of prematurity (ROP) in a recent population of patients and to compare that number with historical data. METHODS: The authors performed a retrospective chart review of all patients treated for ROP within a single practice from 2002-2004. There were 183 eyes from 93 patients. Sufficient data for analysis were available on 112 eyes from 57 patients. Data from these patients were compared to those of patients reported upon in 1991. RESULTS: The average number of laser burns applied to the 112 eyes was 2163. Eyes with zone 1 disease had an average of 3077 spots and those with zone 2 disease had an average of 2072 spots. Greater than three months follow-up was available on 42 eyes from 21 patients. Of those eyes, 90% had complete regression of ROP. In an initial report of laser treatment for ROP by several of the same authors in 1991, the average number of laser burns applied for treatment of ROP was 816. There was a 265% increase in the average number of laser applications from the early study to the present. CONCLUSION: The data indicate that there has been a trend towards more confluent laser treatment to the avascular zone in ROP.

Minimal depression and vision function in age-related macular degeneration.

OBJECTIVE: To evaluate the impact of minimal depression on subjective and objective vision function measures in age-related macular degeneration (AMD). DESIGN: Prospective cross-sectional study. PARTICIPANTS: Two hundred six outpatients with newly diagnosed neovascular AMD in one eye and preexisting AMD in the fellow eye. METHODS: Structured clinical evaluations of visual acuity (VA), contrast sensitivity, vision function, and depression. MAIN OUTCOME MEASURES: The 17-item National Eye Institute Visual Function Questionnaire (NEI VFQ 17), Melbourne Low-Vision Index (MLVI), Chronic Disease Score, and Hamilton Depression Rating Scale. RESULTS: Minimally depressed subjects had significantly worse vision function on both the NEI VFQ 17 and performance-based tasks of the MLVI than nondepressed subjects, independent of severity of VA, contrast sensitivity, and medical status. CONCLUSIONS: Minimally depressed patients with AMD, who would not be considered depressed according to current diagnostic standards, suffer decrements in vision function that cannot be accounted for by the severity of their eye disease or general medical problems. These data emphasize the need to assess depressive symptoms in research studies that use vision function outcome measures and in clinical practice to identify excess vision-related disability in patients with AMD.

Proceedings of the Third International Symposium on Retinopathy of Prematurity: an update on ROP from the lab to the nursery (November 2003, Anaheim, California).

The Third International Symposium on Retinopathy of Prematurity (ROP) was convened with the aim of cross fertilizing the horizons of basic and clinical scientists with an interest in the pathogenesis and management of infants with ROP. Ten speakers in the clinical sciences and ten speakers in the basic sciences were recruited on the basis of their research to provide state of the art talks. The meeting was held November 9, 2003 immediately prior to the American Academy of Ophthalmology meeting; scholarships were provided for outreach to developing countries and young investigators. This review contain the summaries of the 20 platform presentations prepared by the authors and the abstracts of presented posters. Each author was asked to encapsulate the current state of understanding, identify areas of controversy, and make recommendations for future research. The basic science presentations included insights into the development of the human retinal vasculature, animal models for ROP, growth factors that affect normal development and ROP, and promising new therapeutic approaches to treating ROP like VEGF targeting, inhibition of proteases, stem cells, ribozymes to silence genes, and gene therapy to deliver antiangiogenic agents. The clinical presentations included new insights into oxygen management, updates on the CRYO-ROP and ETROP studies, visual function in childhood following ROP, the neural retina in ROP, screening for ROP, management of stage 3 and 4 ROP, ROP in the third world, and the complications of ROP in adult life. The meeting resulted in a penetrating exchange between clinicians and basic scientists, which provided great insights for conference attendees. The effect of preterm delivery on the normal cross-talk of neuroretinal and retinal vascular development is a fertile ground for discovering new understanding of the processes involved both in normal development and in retinal neovascular disorders. The meeting also suggested promising potential therapeutic interventions on the horizon for ROP.

Coats disease: a lifetime disease.

PURPOSE: To document the recurrent nature of Coats Disease. METHODS: This study is a retrospective chart review approved by our Institutional Review Board. Thirteen patients (13 eyes) were diagnosed with Coats Disease starting in 1966. Age, visual acuity, time of onset, method of treatment, and the number and intervals of recurrences were documented. Recurrences were recorded once initial treatment proved successful and most exudates had absorbed. The length of follow-up for each patient and the most recent visual acuity was recorded. RESULTS: The average follow-up period for the 13 patients was 12.4 years with a range from 4.0 to 37.5 years. Eleven patients (85%) were male, two (15%) were female and all had unilateral involvement. The average age at diagnosis was 7.0 years with a range from 9 months to 27 years. Four out of the twelve treated patients (33%) had recurrences, and three of the four had multiple recurrences. The average elapsed time from successful treatment to the first recurrence was 4.3 years with a range from 3.3 to 5.4 years. The average number of recurrences was 3.3. CONCLUSION: Coats Disease can recur so it is important that parents educate any affected children regarding the necessity of follow-up, including throughout their adult years.