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The author shares his views on the fields of study advantageous for medical practitioners such as himself. He admits not realizing how valuable some areas of study would be in his practice as physician. He points to business administration, physics and biochemistry, and psychology as areas of study he prefers. He now relies on his children and their educational pursuits to help him out when his medical practice so demands.

The author reflects on the threats being faced by medical practitioners and optometrists. He notes that managed-care organizations and government regulations have attacked the medical profession. He cites the effects of the proposal to cut 10% in Medicare fees effective July 1, 2008, and the move by Florida Optometrists to push legislation that will allow them to perform intravitreal injections. The author urges ophthalmologists to fight against the proposed legislation and opposes the expansion of optometric practice.

The author reflects on the differences between medical practice in the U.S. and elsewhere in the world. He recounts his conversation with a retinal surgeon from Bulgaria during an educational meeting in Saint Petersburg, Russia. He addresses the limited supply of both diagnostic and therapeutic procedures in some countries. He mentions the membership of the European VitreoRetinal Society (EVRS) in the "Retinal Physician" society.

The author reflects on the importance of understanding patient expectations. He states that when he started practicing several years ago, the options for treatment of most macular diseases were limited and the practicing clinicians always tell their patients that there is nothing that they can do, but someday there will be treatment for the condition. He says when he talks to patients, he always try to find something hopeful in their situation. He adds that patients expect more and offering them the prospect of intervention in the future is appropriate.

The author reflects on the acquisition of new technology instruments, like the autofluorescence imaging for private clinicians. Teaching institutions and large practices only have the sources acquiring new equipment after its introduction, but not for the solo practitioner. The author suggests banding or merging of practice to enable the clinicians to acquire new instruments in coping up with the necessities of clinical practice.

The author recalls the contribution of opthalmologist Judah Folkman to antiangiogenesis. His viewpoint on the therapeutic approach has reportedly gained resistance from other scientists from the beginning. But he was able to prove that his concepts are right after the approval of the drugs such as pegaptanib sodium and ranibizumab and the off-label use of bevacizumab. The author urges clinicians to support current and future clinical trials and to take an active role in the discussions that lead to the development of new clinical trial protocols.

An introduction is presented in which the editor discusses various reports within the issue on topics including role of inflammation in age-related macular degeneration, highlights of The Retinal Physician Symposium held in Boston, Massachusetts, and latest information from Retinal Physicians.

The article offers the author's insights regarding the importance of membership in professional organizations such as American Society of Retinal Specialists (ASRS), American Academy of Ophthalmology (AAO), and Macula Society.

The author reflects on the aftermath of Hurricane Katrina as he prepares to attend the 2007 Annual Meeting of the American Academy of Ophthalmology (AAO) in New Orleans, Louisiana. He believes that what they will see at the AAO venue will not represent the current reality of New Orleans because there are still many parts of the city that are suffering since the tragedy. The author suggests that ophthalmologists re-dedicate themselves to help improve the quality of life of the communities they live in.

The author urges other retinal specialists to extend their education for them to be able to improve their skills in health care. He relates that four years of medical school is not enough for the scientific training of health professionals. He argues that retinal specialists should have a firm foundation in biochemistry, biomechanics, pharmacology and nanotechnology. He suggests ways in which professionals could gain information to deliver the best possible service to patients.

The author reflects on the utilization of pharmacologic therapy for retinal disease specifically on the use of ranibizumab in exudative age-related macular degeneration (AMD). He points out that what is known is its potential to offer significant improvement in vision in some patients with choroidal neovascularization due to AMD. What the people do not know, according to the author, are the distinct features that can definitively predict how patients will respond and how many treatments are required to maintain the effect.

Purpose To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (AMD). Design Randomized, double-masked, sham-controlled, multicenter, clinical trial. Participants A total of 230 participants with neovascular AMD who received ≥3 ranibizumab or bevacizumab injections within the preceding year and requiring treatment at enrollment. Methods Participants received 16 Gray, 24 Gray, or sham SRT. All arms received pro re nata (PRN) ranibizumab for 12 months, with PRN bevacizumab or ranibizumab thereafter. Main Outcome Measures Mean number of PRN injections; best-corrected visual acuity (BCVA); loss of <15 Early Treatment of Diabetic Retinopathy Study letters; change in optical coherence tomography central subfield thickness; and change in angiographic total lesion area and choroidal neovascularization (CNV) area. Results At year 2, the 16 and 24 Gray arms received fewer PRN treatments compared with sham (mean 4.5, P = 0.008; mean 5.4, P = 0.09; and mean 6.6, respectively). Change in mean BCVA was −10.0, −7.5, and −6.7 letters for the 16 Gray, 24 Gray, and sham arms, respectively, with 46 (68%), 51 (75%), and 58 participants (79%), respectively, losing <15 letters. Mean central subfield thickness decreased by 67.0 μm, 55.4 μm, and 33.3 μm, respectively. Mean total active lesion area increased by 1.0, 4.2, and 2.7 mm 2 , respectively. Mean CNV area decreased by 0.1 mm 2 in all groups. An independent reading center detected microvascular abnormalities in 6 control eyes and 29 SRT eyes, of which 18 were attributed to radiation; however, only 2 of these possibly affected vision. An exploratory subgroup analysis found that lesions with a greatest linear dimension ≤4 mm (the size of the treatment zone) and a macular volume greater than the median (7.4 mm 3 ) were more responsive to SRT, with 3.9 PRN injections versus 7.1 in comparable sham-treated participants ( P = 0.001) and mean BCVA 4.4 letters superior to sham ( P = 0.24). Conclusions A single dose of SRT significantly reduces intravitreal injections over 2 years. Radiation can induce microvascular change, but in only 1% of eyes does this possibly affect vision. The best response occurs when AMD lesions fit within the treatment zone and they are actively leaking. [ABSTRACT FROM AUTHOR]

: PurposeTo review and update techniques of posterior segment ophthalmic fundus imaging.: DesignLiterature review and collective experience of the authors.: MethodsThis perspective includes sections on digital imaging, fundus autofluorescence, ultrasonography, angiography, and optical coherence tomography (OCT) -ophthalmoscopy written by leading clinicians and researchers in these areas.: ResultsDigital angiography has become the new standard in the ophthalmic community based upon improved technology which has enhanced resolution, processing time, and ease of image duplication, manipulation, and transmission. A relatively new imaging technique, fundus autofluorescence, highlights lipofuscin deposits and improves our understanding of the metabolic status of the retinal pigment epithelium. Diagnostic ultrasonography continues to be a major adjunct to ocular evaluation where advances now allow for exceptional versatility and portability. High speed angiographic techniques provide detailed visualization of choroidal perfusion which improves our understanding of both normal and pathologic vascular phenomenon. Advances in high-resolution OCT currently under development promise an even more detailed fundus representation. The integration of the scanning laser ophthalmoscope and OCT has produced a dynamic new instrument, the OCT ophthalmoscope, which simultaneously images the fundus in numerous ways with point to point correlation.: ConclusionsOphthalmic imaging technology has revolutionized fundus examination. Currently available systems have contributed significantly to our understanding of the pathophysiology and treatment of various retinal diseases. Future advances promise near histologic resolution of retinal structures as well as real-time image manipulation and instantaneous transmission world-wide. [Copyright &y& Elsevier]

To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial. Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA). Patients with GA secondary to age-related macular degeneration (AMD), n = 246. Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period. Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity. Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31–555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P < 0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti–vascular endothelial growth factor (VEGF) therapy. Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria. [ABSTRACT FROM AUTHOR]

Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. Prospective, multicenter, randomized, sham-controlled phase 2 study. Two hundred forty-six patients with GA. Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9–49; P = 0.008) and 20% (95% CI, 0–40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further. [ABSTRACT FROM AUTHOR]

Purpose: Identify predictors for response to anti‐vascular endothelial growth factor (VEGF) therapy in patients with neovascular (wet) age‐related macular degeneration (nAMD). Methods: Retrospective, post hoc analysis of VIEW 1/2. Patients were randomized 1:1:1:1 to 0.5 mg intravitreal aflibercept (IVT‐AFL) injection every 4 weeks (0.5q4); 2 mg IVT‐AFL every 4 weeks (2q4); 2 mg IVT‐AFL every 8 weeks (2q8) after an initial three injections at weeks 0, 4 and 8 or 0.5 mg intravitreal ranibizumab every 4 weeks (0.5q4). Results: 1815 patients [IVT‐AFL 2q4 (n = 613); IVT‐AFL 2q8 (n = 607); ranibizumab 0.5q4 (n = 595)] were included. Baseline demographics/characteristics were evenly balanced. Younger age (49–69 years), lower visual acuity (VA) [10.0–≤45.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] and smaller choroidal neovascularization (CNV) size [0.0–≤3.1 disc areas (DA)] at baseline were associated with the most vision gain (≥15 letters) over 52 weeks (all nominal p < 0.0001).Younger age, higher baseline VA (>64.0–≤83.0 letters) and smaller CNV size were associated with a VA ≥20/40 at week 52. Predominantly classic CNV at baseline (nominal p = 0.0007), older age (≥90 years), lower baseline VA (10.0–≤ 45.0 ETDRS letters) and larger CNV size (>10.1–≤32.6 DA) were all associated with a VA ≤20/200 at week 52 (all nominal p < 0.0001). Along with treatment (nominal p < 0.0001), lower VA (p = 0.0166) and smaller central retinal thickness (both nominal p = 0.0190) were predictors for dry retina development. Conclusion: Younger age, lower VA and smaller CNV size at baseline were all associated with greater vision gains over 52 weeks while younger age, higher VA and smaller CNV size at treatment start were more likely to achieve best‐corrected VA 20/40 or better after a year's treatment, suggesting the benefit of early anti‐VEGF treatment. [ABSTRACT FROM AUTHOR]

Purpose To compare efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for diabetic macular edema (DME) over 3 years. Design Two similarly designed phase 3 trials: VISTA DME and VIVID DME . Participants Patients (eyes; n = 872) with central-involved DME. Methods Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser control. From week 24, if rescue treatment criteria were met, IAI patients received active laser, and laser control patients received IAI 2q8. From week 100, laser control patients who had not received IAI rescue treatment received IAI as needed per retreatment criteria. Main Outcome Measures The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at week 52. We report the 148-week results. Results Mean BCVA gain from baseline to week 148 with IAI 2q4, IAI 2q8, and laser control was 10.4, 10.5, and 1.4 letters ( P < 0.0001) in VISTA and 10.3, 11.7, and 1.6 letters ( P < 0.0001) in VIVID, respectively. The proportion of eyes that gained ≥15 letters from baseline at week 148 was 42.9%, 35.8%, and 13.6% ( P < 0.0001) in VISTA and 41.2%, 42.2%, and 18.9% ( P < 0.0001) in VIVID, respectively. Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 versus those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale (DRSS) score in both VISTA (29.9% and 34.4% vs. 20.1% [ P = 0.0350, IAI 2q4; P = 0.0052, IAI 2q8]) and VIVID (44.3% and 47.8% vs. 17.4% [ P < 0.0001 for both]). In an integrated safety analysis, the most frequent ocular serious adverse event was cataract (3.1%, 2.1%, 0.3% for 2q4, 2q8, and control). Conclusions Visual improvements observed with both IAI regimens (over laser control) at weeks 52 and 100 were maintained at week 148, with similar overall efficacy in the IAI 2q4 and IAI 2q8 groups. Treatment with IAI also had positive effects on the DRSS score. Over 148 weeks, the incidence of adverse events was consistent with the known safety profile of IAI. [ABSTRACT FROM AUTHOR]

Purpose To compare efficacy and safety of 2 dosing regimens of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for diabetic macular edema (DME). Design Two similarly designed, randomized, phase 3 trials, VISTA DME and VIVID DME . Participants Patients (eyes; n=872) with type 1 or 2 diabetes mellitus who had DME with central involvement. Methods Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser control. Main Outcome Measures The primary end point was mean change from baseline in best-corrected visual acuity (BCVA) at week 52. This report presents the 100-week results including mean change from baseline in BCVA, proportion of eyes that gained ≥15 letters, and proportion of eyes with a ≥2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Results Mean BCVA gain from baseline to week 100 with IAI 2q4, IAI 2q8, and laser control was 11.5, 11.1, and 0.9 letters ( P < 0.0001) in VISTA and 11.4, 9.4, and 0.7 letters ( P < 0.0001) in VIVID, respectively. The proportion of eyes that gained ≥15 letters from baseline at week 100 was 38.3%, 33.1%, and 13.0% ( P < 0.0001) in VISTA and 38.2%, 31.1%, and 12.1% ( P ≤ 0.0001) in VIVID. The proportion of eyes that lost ≥15 letters at week 100 was 3.2%, 0.7%, and 9.7% ( P ≤ 0.0220) in VISTA and 2.2%, 1.5%, and 12.9% ( P ≤ 0.0008) in VIVID. Significantly more eyes in the IAI 2q4 and 2q8 groups versus those in the laser control group had a ≥2 step improvement in the DRSS score in both VISTA (37.0% and 37.1% vs. 15.6%; P < 0.0001) and VIVID (29.3% and 32.6% vs. 8.2%; P ≤ 0.0004). In an integrated safety analysis, the most frequent serious ocular adverse event was cataract (2.4%, 1.0%, and 0.3% for 2q4, 2q8, and control). Conclusions In both VISTA and VIVID, the 52-week visual and anatomic superiority of IAI over laser control was sustained through week 100, with similar efficacy in the 2q4 and 2q8 groups. Safety in these studies was consistent with the known safety profile of IAI. [ABSTRACT FROM AUTHOR]

Purpose A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME). Design Two similarly designed, double-masked, randomized, phase 3 trials, VISTA DME and VIVID DME . Participants We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement. Methods Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation. Main Outcome Measures The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography. Results Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters ( P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters ( P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥15 letters were 41.6% and 31.1% versus 7.8% ( P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% ( P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm ( P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm ( P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration–defined arterial thromboembolic events and vascular deaths, were similar across treatment groups. Conclusions At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated. [ABSTRACT FROM AUTHOR]

Purpose: To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period. Design: Two randomized, double-masked, active-controlled, phase 3 trials. Participants: Two thousand four hundred fifty-seven patients with neovascular AMD. Methods: From baseline to week 52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2 mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks. Main Outcome Measures: Proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost <15 letters from baseline); change from baseline in BCVA. Results: Proportions of eyes maintaining BCVA across treatments were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. Mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96 (44.6% to 54.4%), and more 2q4 eyes were without fluid at weeks 52 and 96 than Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9–15.9] and 9.0% [95% CI, 3.0–15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2 injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52 through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group (differences of −0.64 [95% CI, −0.89 to −0.40] and −0.55 [95% CI, −0.79 to −0.30]; P < 0.0001, post hoc analysis). Incidences of Antiplatelet Trialists' Collaboration–defined arterial thromboembolic events were similar across groups (2.4% to 3.8%) from baseline to week 96. Conclusions: All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks. The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing. [Copyright &y& Elsevier]