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Closing Comments

Dr. Kiss: We are seeing a revolution in the diagnosis and treatment of diabetic eye disease. Ultrawide-field imaging has now replaced the traditional seven-standard fields as the preferred method for fundus evaluation of our diabetic patients. Pharmacotherapy, in the form of anti-VEGF intravitreal injections, is slowly replacing laser as the first line therapy for DR and DME in many of our patients. Despite these advances, compliance with follow-up from all our diabetic patients will nonetheless remain an important determinant of their visual outcome.

Dr. Coney: The most important factor that guides my decision to begin anti-VEGF agents in DR patients is the level of severity. The availability of these agents has shifted our focus from thermal treatment to modulating the pathophysiology of the disease. Newer imaging modalities may change the landscape on when and how we initiate our therapy. Emerging studies will continue to refine our management and tailor individualized treatments.

Lost to Follow-Up

The Potential Consequences for Treatment Interruptions Among Patients Treated Solely With Anti-VEGF Therapy

While the use of anti-VEGF therapy for treatment of diabetic retinopathy (DR) has shown promise for regressing DR severity, patients’ adherence to recommended follow-up may be an important determinant for the ultimate success of treatment.

During the AAO Annual Meeting, Mark W. Johnson, MD, presented data suggesting that eyes with proliferative DR treated solely with anti-VEGF injections have worse anatomic and functional outcomes after losses to follow-up compared to eyes that receive PRP.1

  • Investigators reviewed records of 13 eyes of 12 patients treated exclusively with anti-VEGF therapy and who had a temporary loss to follow-up:
    • Mean age, 56.6 ± 10.4 years; 50% (6/12) women.
    • 100% type 2 diabetes mellitus (median duration = 19 years); mean hemoglobin A1c, 9.5 ± 2.5%.
  • Mean treatment duration was 16.8 ±21.7 months and patients received a mean 7.1 ± 6.4 injections.
    • Median duration of treatment interruption was 12 months (range, 3-25 months).
  • New complications after treatment interruption:
    • Vitreous hemorrhage, n = 9 (69%);
    • Neovascular glaucoma, n = 5 (38%); and
    • Traction retinal detachment, n = 4 (31%).
  • Ten patients (77%) lost three or more lines of VA, including 6 (46%) with final VA of hand motion or worse.
    • Mean VA before hiatus 0.61 ± 0.41 versus mean VA after hiatus 1.53 ± 1.02 ( P = .013).
  • Author’s conclusion: The potentially severe consequences of interruptions in anti-VEGF therapy should be carefully considered when making initial treatment decisions.

1. Johnson MW, Wubben TJ, Hsu J. Anti-VEGF therapy for diabetic retinopathy consequences of inadvertent treatment interruptions. Presented at the Annual Meeting of AAO. October 27-30, 2018; Chicago, Illinois.

Dr. Chiang: We are in the midst of a paradigm shift in the management of DR. Our diagnostic capabilities continue to improve; wide-field imaging and OCT-A represent advances that increase our ability to detect pathology. Artificial intelligence and telemedicine hold the promise of enabling early detection across a population. As far as therapeutics, the mainstay for decades was laser. We now have clinical trial data to support the use of anti-VEGF therapy as a capable and noninferior treatment modality that can achieve impressive results in terms of disease regression. However, patient education and compliance remain an issue since DR is progressive, particularly when utilizing anti-VEGF therapy over laser. Future treatments possessing greater durability will likely help alleviate this concern. In the meantime, retinal physicians should stay up-to-date on emerging data and tailor the treatment plan to the patient to the best of their ability.

Dr. Wykoff: Clearly, there is tremendous variation in how each of us employs anti-VEGF agents in the management of DR. In particular, many management questions remain to be clarified regarding the use of imaging, the timing of initiation of treatment, and the follow-up protocols while on treatment for high-risk NPDR eyes without DME. I think we can all agree that, currently, decisions about when and how to initiate therapy for DR are highly individualized to the specific needs and desires of each patient. Ongoing trials, such as PANORAMA and the DRCR.net Protocol W, will continue to shape these discussions.

Thank you all for your participation.

1. Brown DM, Nguyen QD, Marcus DM, et al; RIDE and RISE Research Group. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology. 2013;120(10):2013-2022.

2. Heier JS, Korobelnik JF, Brown DM, et al. Intravitreal aflibercept for diabetic macular edema: 148-week results from the VISTA and VIVID studies. Ophthalmology. 2016;123(11):2376-2385.

3. Gross JG, Glassman AR, Jampol LM, et al; Writing Committee for the Diabetic Retinopathy Clinical Research Network. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical Trial. JAMA. 2015;314(20):2137-2146.

4. Gross JG, Glassman AR, Liu D, et al; Diabetic Retinopathy Clinical Research Network. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2018;136(10):1138-1148.

5. Wykoff C. Intravitreal aflibercept for moderately severe to severe nonproliferative diabetic retinopathy (NPDR): the phase 3 PANORAMA study. Presented at the ASRS Annual Meeting, July 20-25, 2018; Vancouver, BC.

6. Liu Y, Yang J, Tao L, et al. Risk factors of diabetic retinopathy and sight-threatening diabetic retinopathy: a cross-sectional study of 13,473 patients with type 2 diabetes mellitus in mainland China. BMJ Open. 2017;7(9):e016280.

7. Hur KY, Kim MS, et al. Risk factors associated with the onset and progression of posttransplantation diabetes in renal allograft recipients. Diabetes Care. 2007;30(3):609-615.

8. Zhang R, Li Y, Zhang S, et al. The association of retinopathy and plasma glucose and hba1c: a validation of diabetes diagnostic criteria in a Chinese population. J Diabetes Res. 2016;2016:4034129.

9. Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology. 1991;98(5 Suppl):766-785.

10. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.

11. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.

12. American Diabetes Association. Standards of medical care in diabetes–2017. Diabetes Care. 2017;40 Suppl 1:S48-S52.

13. The Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes. 1995;44(8):968-983.

14. Aiello LP, Odia I, Glassman AR, et al; Diabetic Retinopathy Clinical Research Network. Comparison of Early Treatment Diabetic Retinopathy Study standard 7-field imaging with ultrawide-field imaging for determining severity of diabetic retinopathy. JAMA Ophthalmol. 2018.

15. Wykoff CC. Intravitreal aflibercept for moderately severe to severe nonproliferative diabetic retinopathy (NPDR): the phase 3 PANORAMA study. Presented at ASRS, July 24, 2018; Vancouver, BC.

author
Charles C. Wykoff, MD, PhD, Moderator

Charles C. Wykoff, MD, PhD, Moderator

  • Director of Research, Retina Consultants of Houston, Houston, Texas
  • Deputy Chair of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas
  • ccwmd@houstonretina.com
  • Financial disclosures: Consultant/Grant Support (Alimera, Allergan, Bayer, Clearside Biomedical, Genentech, Kodiac, Novartis, Regeneron Pharmaceuticals, Inc.)
author
Szilárd Kiss, MD
  • Chief, Retina Service; Director, Clinical Research; Director, Teleophthalmology; Director, Compliance; Associate Professor of Ophthalmology, Weill Cornell Medical College, New York City, New York
  • Associate Attending Physician at New York Presbyterian Hospital, New York City, New York
  • szk7001@med.cornell.edu
  • Financial disclosures: Advisory Board (Alcon, Adverum Biotechnologies Inc., Alimera Sciences, Allergan, Biomardin Pharmaceutical, Inc., Genentech, Novartis, Optos, Regeneron Pharmaceuticals, Inc., Regenxbio, Inc., Spark Therapeutics); Consultant (Alcon, Adverum Biotechnologies Inc., Alimera Sciences, Allergan, Biomardin Pharmaceutical, Inc., Fortress Biotech, Genentech, Novartis, Optos, Regeneron Pharmaceuticals, Inc., Regenxbio, Inc., Spark Therapeutics); Grant Support (Genentech, Optos, Spark Therapeutics); Honoraria (Alcon, Adverum Biotechnologies Inc., Alimera Sciences, Allergan, Biomardin Pharmaceutical, Inc., Fortress Biotech, Genentech, Novartis, Optos, Regeneron Pharmaceuticals, Inc., Regenxbio, Inc., Spark Therapeutics); Investigator (Genentech, Regeneron Pharmaceuticals, Inc.); Stock Options (Adverum Biotechnologies, Inc., Fortress Biotech, Regenxbio, Inc.)
author
Joseph M. Coney, MD
  • Vitreoretinal Surgeon, Retina Associates of Cleveland, Cleveland, Ohio
  • Clinical Senior Instructor, Case Western Reserve University School of Medicine, Cleveland, Ohio
  • jconey@retina-assoc.com
  • Financial disclosures: Consultant (Alimera Sciences, Allergan, Genentech, Regeneron Pharmaceuticals, Inc.; Grant Support (Aerpio Pharmaceuticals, Hoffman-La Roche)
author
Allen Chiang, MD
  • Faculty Member, Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania
  • Partner, Mid Atlantic Retina, Philadelphia, Pennsylvania
  • Assistant Professor of Ophthalmology, Thomas Jefferson University, Philadelphia, Pennsylvania
  • Member of the Retina Today editorial advisory board
  • achiang@midatlanticretina.com
  • Financial disclosures: Research Support (Apellis Pharmaceuticals; Genentech, Regeneron Pharmaceuticals, Inc.)
author
Caroline R. Baumal, MD
  • Associate Professor of Ophthalmology, New England Eye Center, Boston, Massachusetts
  • Director of ROP Service, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
  • cbaumal@tuftsmedicalcenter.org
  • Financial disclosures: Consultant/Speaker (Carl Zeiss Meditec, Genentech)