Caroline Helwick

June 25, 2017

WASHINGTON, DC — One treatment clearly does not fit all patients with central serous retinopathy (CSR). Determining which approach to try on which patient, and getting it paid for, is a challenge for eye care practitioners, researchers reported here at Optometry's Meeting by the American Optometric Association (AOA).

"CSR can be self-limited, so you can observe at first, but you can't just let the disease linger," Mohammad Rafieetary, OD, told Medscape Medical News.

Dr Rafieetary and colleagues from the Charles Retina Institute in Germantown, Tennessee, described their experience in treating CSR and reviewed the literature on the topic in a "Top 5 Poster" presentation. The study's first author was Roya Attar, OD, MBA.

CSR is a chorioretinal disease characterized by the accumulation of subretinal fluid in the posterior pole. It affects approximately 10 men and 2 women per 100,000 people, and whereas most acute cases spontaneously resolve, CSR can become chronic and poses a risk for permanent anatomic and functional loss, the authors noted.

"The challenge is that treatment options are effective in some patients but not in others. Even some that work initially will not work in recurrent cases," Dr Rafieetary said. "In acute cases, you can observe for a month or two, and if it worsens, you may want to discuss treatment options with patients: pros and cons, costs, insurance coverage."

His first treatment recommendation is usually "the least expensive one and the treatment with the least potential for side effects," he said in an interview.

Variety of Treatment Approaches

Many treatment strategies have been explored for chronic cases, including photo dynamic therapy (PDT) after verteporfin (Visudyne) administration, focal laser, intravitreal injections of compounds targeting the vascular endothelial growth factor (anti-VEGF agents), and systemic oral medications, especially aldosterone antagonists.

"But with the exception of an orphan drug designation for verteporfin, there is currently no other approved treatment, and no international consensus as to the optimal treatment protocol," Dr Rafieetary said.

Six Cases, Different Treatments

The retina specialists presented six cases of CSR in which different management options were successful. After 1 year of follow-up or longer, the final outcome in all patients was substantial improvement in, or complete resolution of, subretinal fluid. These cases validated the benefit of the various treatments and showed the utility of imaging strategies, including optical coherence tomography (OCT), fundus autofluorescence, fluorescein angiography, and indocyanine green angiography in management.

"Our cases demonstrate that there is no clear-cut treatment for CSR; however, in each case, an appropriate course of treatment and follow-up care are necessary for an optimal outcome," he said.

Case: Successful Treatment With Eplerenone

One case involved a 41-year-old man whose chief complaint was constant blurry vision in the OS (left eye) for 2 weeks. Best corrected visual acuity (BCVA) was 20/20 OD (right eye) and 20/30 OS. Fundus exam showed elevated area inferior to fovea in OD, and large central serous retinal detachment (SRD) with a juxta foveal yellow color lesion in OS. OCT imaging showed 1200 μM serous pigment epithelial detachment (PED) about 350 μM inferior to fovea in OD. OS had large SRD with juxta foveal and subfoveal shallow PEDs. A thicker-than-average choroid was noted as well in both eyes. The diagnosis of CSR was confirmed.

As a result of his short duration of symptoms, the patient was initially monitored without treatment. At 1 month follow-up, BCVA was 20/20 OD and OS. OCT showed resolution of serous PED in OD and in OS, and the area of SRD had become shallower. Central retinal thickness (CRT) had decreased from 858 μM to 373 μM, but had enlarged in size, shifting fluid inferiorly. As a result of signs of improvement, the patient was monitored for an additional month.

At 2 months' follow-up, BCVA 20/20 OD and 20/25 OS was noted. OCT in OD was still free of serous fluid. SRD in OS had decreased in size, but CRT had increased to 436 μM. No increased fluid was noted around PED in a superior direction. At this time, the physicians started oral eplerenone (Inspra) 25 mg/day to attempt faster resolution of the SRD. One month later, BCVA was again 20/20 OD and OS. There was partial recurrence of serous PED in OD with no overlying sensory detachment. OS had almost complete resolution of SRD, with CRT reduced to 252 μM. The patient had no adverse effects from eplerenone.

Laser Therapies

The authors also described their literature search and their own experience with laser treatment strategies.

Photodynamic therapy, after administration of verteporfin, is the most widely accepted treatment for CSR. It is thought to work by mechanical closure of choroidal capillaries, which reduces vascular leakage and resolves the SRD. Eleven major studies showed PDT to be an effective treatment, and it received the US Food and Drug Administration's orphan drug designation for CRS in 2012.

"Even with this, however, we have problems getting insurers to cover PDT," Dr Rafieetary said. "We've had cases where insurers have paid, then 3 months later they audited the chart, called the treatment experimental, and asked for their money back. This puts patients and practices in a tough spot."

The cost of verteporfin alone is about $1600, not including the expense of the laser and staff time. When his group recommends PDT, patients are often asked to pay up front, and then deal with their insurance company themselves (with "paperwork" provided by the office), he said.

The fact that the 693-nm Coherent Lumenis Opal PDT laser is no longer in production is another stumbling block to PDT, as the laser is required to activate verteporfin. Not all facilities, therefore, can offer this treatment, which, if cost were not an issue, would often be Dr Rafieetary's first choice, he said.

Another laser therapy, focal photocoagulation, uses a variety of thermal lasers (xenon, krypton, and more recently argon) and subthreshold lasers, such as Pascal and micropulse yellow lasers, to stop leakage. Although some studies have not shown benefit for long-term argon laser photocoagulation, it is a widely accepted treatment in selected cases with small extrafoveal lesions, he said.

Intravitreal Anti-VEGF

Intravitreal anti-VEGF therapy has gained favor in treating CSR. Although CSR may not be a VEGF-mediated disease, this approach is thought to work by decreasing choroidal vascular permeability.

The authors reviewed 19 international studies, most of which were prospective, involving 366 total patients with acute, chronic, or recurrent CSR treated with intravitreal bevacizumab (Avastin) or ranibizumab (Lucentis) compared with 84 control patients. In all but one study, intravitreal anti-VEGF produced statistically significant improvements in mean BCVA and mean CRT. On the basis of this review, Dr Rafieetary and his team concluded that intravitreal anti-VEGF injections result in visual and anatomic improvement and reduce the duration and recurrence of CSR.

"Patients with smaller lesions, better vision, and thick choroid may respond better than those with florid serous fluid and vision that has already dropped," he added.

Again, he noted, cost is an issue for the off-label use of these compounds.

Systemic Treatments

The role of exogenous glucocorticoids in the pathogenesis of CSR is well known, which forms the basis for using mineralocorticoid antagonists or aldosterone antagonists, including spironolactone (Aldactone) and eplerenone (Inspra).

Spironolactone was initially approved for treating hypertension and heart failure. Multiple studies show it significantly reduces persistent subretinal fluid. Eplerenone is a less potent but more selective mineralocorticoid antagonist; therefore, it is associated with fewer hormonal adverse effects. A number of studies have shown that 25 mg/day can reduce serous fluid.

Although this is often Dr Rafieetary's first treatment choice, some clinicians have been skeptical, he said. "Their first response to using aldosterone antagonists was 'This is mad science.... I'm not buying it!' But anecdotally we see resolution of CRS with these agents, and the literature supports this."

Other oral agents have been tried with varying degrees of success. "When medical treatment is considered, practitioners should consider risks and benefits, contraindications, adverse effects, and conduct proper follow-up," he added.

Diagnostic Guidance

Although there is little in the way of formal diagnostic guidance, Dr Rafieetary and his team offered some tips from their own practice:

  • Fluorescein angiography can produce distinctive findings in the acute presentation. Characteristic presentations include the classic smoke stack, ink blot, or multifocal leakage. In chronic CSR, such leakage may not be noted, but there may be staining of the altered RPE.

  • Not only does indocyanine green angiography demonstrate and confirm involvement of the choroid in CRS but also the late-phase indocyanine green angiography findings are particularly helpful in selecting treatment locations and options.

  • Fundus autofluorescence imaging in acute CSR usually shows hypo-autofluorescence delineation by the serous retinal detachment, whereas chronic cases show a variable degree of hyperautofluorescence, usually mottled in appearance associated with altered and damaged retinal pigment epithelium.

  • OCT angiography, a newer technique, will be gaining a role in diagnosis and management of CRS as it becomes used more in clinical practice.

Beth Sparrow, OD, associate professor at the Southern College of Optometry, Memphis, Tennessee, commented that Dr Rafieetary and his team, to whom she often refers patients, are "more than experts in this subject."

She agreed, "There is no one way to treat CSR," but similar to Dr Rafieetary, Dr Sparrow has been encouraged by the outcomes she has seen with eplerenone. She told Medscape Medical News that she recently used this agent on a patient with CSR for more than a year's duration. "Typically, we've heard that vision will not be that diminished with CSR, but this patient's acuity was very bad; it had decreased to 20/400. We treated with eplerenone, and within 5 days she had improvement," she said.

"Some patients I do watch, although in all honesty, until recently, I watched patients more, because that is how we were taught," she said. "Most do resolve, but it may take some time. I think it's also patient-dependent."

Conclusion

Patients being followed without treatment should be screened clinically and with appropriate diagnostic testing to ensure accurate diagnosis, and monitored closely to determine when to initiate treatment and to ensure optimal results. Other factors may contribute to CSR and to the results obtained with treatment, such as systemic conditions, and these should be addressed.

Eye care physicians "must stay abreast" of the potential benefits and risks of current and alternative treatment options for CSR, which carries the potential for functional vision loss, the authors advised.

Dr Rafieetary and Dr Sparrow have disclosed no relevant financial relationships.

Optometry's Meeting by the American Optometric Association (AOA): Abstract 44. Presented June 23, 2017.

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