The burden on young, working diabetic patients who struggle to endure frequent intravitreal injections is multifactorial.
The most recent data reported by the Centers for Disease Control and Prevention the American Diabetes Association reveal that, in 2015, the prevalence of diabetes in the United States was 30.3 million or 9.4% of the population.(1)
The rates of diagnosed diabetes among non-Hispanic white adults is 7.4% compared with 12.1% of Hispanic adults.(2) A further ethnicity breakdown among Hispanic adults shows the rates as:
• 8.5% for Central and South Americans
• 9.0% for Cubans
• 13.8% for Mexican Americans
• 12.0% for Puerto Ricans
Diabetic eye disease is a leading cause of vision loss in individuals aged 20 to 74,(3) and diabetic macular edema (DME), left untreated, is the leading cause of blindness in diabetic patients. The diabetes Control and Complications Trial reported that 27% of patients affected by type 1 diabetes develop DME within 9 years of onset.(4) Other studies have shown that in patients with type 2 diabetes, the prevalence increased from 3% to 28% within 5 years of diagnosis to 20 years after the onset.
From the 1980s to 2010, focal/grid laser photocoagulation was the standard of care for treating macular edema, reducing the risk of vision loss. More recently, intravitreal injections of anti-vascular endothelial growth factor agents have been widely used.
A recent practice move to San Luis Obispo County in Central California brought me face to face with what it is like for diabetes patients struggling to keep up with their treatment for eye disease. SLO is one of California’s original counties, located along the Pacific Coast about halfway between Los Angeles and San Francisco. The inland region includes vast agricultural areas, with farming and tourism among the key industries in this heavily Hispanic population.
I see many patients with poorly controlled diabetes who have chronic bilateral, eye disease. These are young, working individuals in their 30s and 40s who are raising families and often lack stable medical insurance. Not only is it expensive to treat patients indefinitely with frequent anti-VEGF injections, there is an associated risk, however small, of adverse events including infection or possibly inadvertently perforating the lens. Shots are uncomfortable, and they can make patients apprehensive. The agents require a significant long-term commitment to therapy on the part of the patient. Managing a patient’s treatment and testing schedule is a complex and burdensome exercise for entire families.
Therefore, my goal for these individuals is to use all the therapies at my disposal to provide the most effective treatment regimen that also allows me to reduce the number and frequency of injections.
LOSING SIGHT OF LASER
I believe that, in the intravitreal injection era, we underutilize laser therapy. The use of the laser source as a method of treatment for DME was first evaluated in a protocol in the Diabetic Retinopathy Study (DRS) in 1981.(5) The next clinical trial of diabetic retinopathy, the Early Treatment Diabetic Retinopathy Study (ETDRS) suggested that scatter laser photocoagulation should be considered for all eyes with severe nonproliferative diabetic retinopathy or worse. Regarding macular edema treatment, the ETDRS, further concluded that focal or grid laser photocoagulation was effective.(6) Despite the ETDRS study’s being the gold standard in the classification and treatment of diabetic retinopathy and macular edema, it seems that DME photocoagulation laser treatment has been replaced by the new intravitreal drugs.
TISSUE-SPARING TECHNOLOGY
Newer tissue-sparing laser technology can treat disease using thermal stress but without causing collateral tissue damage. The original approach, transpupillary thermotherapy, was difficult to reliably titrate. A micropulse laser at the same wavelength was then applied to heat the retina below clinically detectable damage, and clinical trials demonstrated this therapy’s efficacy in the macula. Advantages of tissue-sparing treatment include the absence of scotoma and scarring, the ability to treat foveal areas, and possibility of retreatment. This approach was originally hard to tritrate, however. It was time consuming to manually apply hundreds of spots and difficult to perform without visible marks of the treatment.
Semi-automatic pattern scanning laser photocoagulation (PASCAL; Topcon) was developed for providing rapid, precise, and computer-guided laser treatment. Automatic advancement of the patterns allows for an exact abutment of the treatment areas on the retina and trabecular meshwork. The surgeon can select from several treatment patterns with adjustable number of spots and their density.
ENDPOINT MANAGEMENT
To provide exact dosimetry for the retinal therapy, Topcon developed Endpoint Management (EpM) technology. The surgeon applies the laser to produce a barely-visible retinal lesion, using a titrated amount of energy applied to the retinal pigment epithelium (RPE). EpM, the laser algorithm, then allows the application of laser therapy at tissue-sparing settings, which in my hands, provides nondamaging results. Operating below the damage threshold and within these parameters allows the application of high-density patterns to boost clinical efficacy, treatment through the fovea, and the possibility of retreatment.
PASCAL laser with EpM has been shown to be associated with little to no discomfort for patients, so they are more satisfied with their treatment, and the procedure is quick as well. Although the visual improvement might not show up on the eye chart, subjectively, my patients say their vision is slightly clearer within a couple of days of laser therapy; another advantage.
I prefer to treat with laser using EpM in patients with nonfoveal DME, and I use it in conjunction with monthly anti-VEGF injections for fovea-involving DME. It is important to monitor OCT scans closely in these patients to evaluate the patient’s response; I am looking for a trend toward decreasing central macular thickness. One should be aware that, other factors can cause thickness on OCT, so I take care to correctly identify edema. Using FA in conjunction with OCT is crucial to properly differentiate between truly leaking vascular disease and ischemic or mechanical thickening and better direct treatment.
PROTOCOL FOR YOUNG DIABETIC PATIENTS
In patients with center-involved DME, I perform a baseline FA and OCT and administer a loading dose of six injections with an anti-VEGF agent. At this stage, I evaluate their response with repeat FA and OCT. If it is not trending in the right direction, I add a steroidal agent, which typically are associated with a positive trend in decreased CMT and leakage on FA. Once I see a trend, I seek to extend the treatment interval for my patients. I apply EpM laser treatment, and continue with a treat-and-extend strategy for anti-VEGF injections. Pars plana vitrectomy can be considered when there is a clear component of vitreomacular traction or macular puckering that compromises the full effect of anti-VEGF treatment.
OTHER EXPERIENCE
Victor H. Gonzalez has reported his experience with EpM laser in patients with center-involved DME. He evaluates the patient after three anti-VEGF; if it is good he does not use the laser. He follows with three more injections until the macula normalizes and the visual acuity no longer improves. He begins a treat-and-extend regimen on these patients. If after six injections there is not a significant reduction in center-involved DME, he reevaluates and performs FA. If the visual acuity is 20/50 or worse, he tries three aflibercept (Eylea; Regeneron) injections. If there is a favorable response, he continues until the anatomy normalizes and visual acuity stabilizes. At that point, he adds a steroid if there is still center involved DME. If there is still some edema that satisfies the ETDRS criteria and does not involve the center, Dr. Gonzalez said, he will use the PASCAL laser in those areas of activity.
Dr. Gonzalez conducted a retrospective study to see if he could identify the patients who were likely to be unresponsive or partially responsive to long-term anti-VEGF therapy.7 The significant takeaway was that, after three injections, it is essential to reassess DME patients to ascertain whether other interventions need to be considered. At that time point, he found he could determine how the patient was going to do at 1, 2, and 3 years. He noted that the findings backup his regimen: reevaluate patients after three injections to determine if continued injections will be effective alone of if adjunctive laser therapy with EpM is warranted.
CONCLUSION
Combining anti-VEGF with steroid injections, EpM laser, and pars plana vitrectomy can decrease the overall long-term treatment burden on diabetic patients receiving anti-VEGF injections. Laser therapy is safer, faster, more comfortable, and is not associated with the same kind of risks as intravitreal treatment. It may allow patients to prolong the time intervals in between visits.
In my experience with a young working class diabetic population who have poorly controlled diabetes and bilateral retinal disease—plus a lack of stable medical insurance—it has become obvious that surgeons need to develop effective strategies that prolong treatment intervals or graduate patients from the chronic need for anti-VEGF. Adding laser therapy to the treatment algorithm is a valuable option and considers patients’ needs.
Ragui Sedeek, MD, is in practice at Elite Eye Care, Santa Maria, California.
He can be reached at Dr.Sedeek@shepardeye.com
1. New CDC report: More than 100 million Americans have diabetes or prediabetes. Press Release. July 18, 2017. https://www.cdc.gov/media/releases/2017/p0718-diabetes-report.html. Accessed March 27, 2018.
2. American Diabetes Association. Statistics About Diabetes Overall Numbers, Diabetes and Prediabetes. http://www.diabetes.org/diabetes-basics/statistics. Accessed March 27, 2018.
3. Resnikoff S, Pascolini D, Etya’ale D, et al. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004;82(11):844-851.
4. National Eye Institute, National Institutes of Health, US Department of Health and Human Services. Diabetic retinopathy: what you should know. http://www.nei.nih.gov/health/diabetic/diabeticretino.pdf. Accessed October 21, 2013
5. Indications for photocoagulation treatment of diabetic retinopathy Diabetic Retinopathy Study Report no 14.The Diabetic Retinopathy Study Research Group. . Int Ophthalmol Clin. 1987;Winter 27:239-253.
6. Early Treatment Diabetic Retinopathy Study Research Group. Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline ETDRS report no 17. Arch Ophthalmol. 1995;113:1144-1155.
7. Gonzalez VH, Campbell J, Holekamp NM, et al. Early and late Anti-VEGF Response in diabetic macular edema. Am J Ophthalmol. 2016;172:72-79.