ASRS 2018: AMD2 — Dry AMD

Lekha Mukkamala, MD
Vitreoretinal Surgery Fellow
University of California, Davis

The second half of the morning on non-neovascular AMD kicked off with discussion of the Chroma and Spectri studies. Although lampalizumab was not found to have any effect on the progression of geographic atrophy (GA), Dr. Regillo showed data from the sham cohorts that provided useful information. The adjusted mean data, which corrected for any potential imbalance of factors, revealed that the low luminance deficit (defined by the difference in best corrected visual acuity and the low luminance visual acuity) was associated with greater progression of GA. Objective anatomic factors that were also associated with progression were larger baseline GA, nonsubfoveal location, and multifocal nature.  Demographic factors that showed a small trend toward more progression after adjustment were female gender and tobacco use.


The Chroma and Spectri databases also provided a patient population for identification of certain previously-identified high risk SNP’s (single nucleotide polymorphisms), which involve the complement system and HTRA2 gene. Data analysis revealed that none of the SNPs were associated with GA growth, but some trends were seen with the HTRA2 gene. Although these findings are limited by the fact that the analysis was performed on a very specific patient population and only on a small portion of the genome, the data revealed that phenotypic appearances have a greater influence on the degree of GA growth compared to genotypes. In Dr. Csaky’s words, “phenotype trumps genotype.”

Next Dr. Steinle discussed the 18-month findings of the largest phase II study on GA, FILLY, which is to assess the effect of APL-2 (a complement C3 inhibitor) on GA progression, with varying treatment frequency. APL-2 was found to slow the rate of lesion growth in the 2nd6 months with either monthly or bimonthly injections. When the treatment was stopped, the rate of growth of GA was again similar to that without treatment. The drug is due to go into paired phase 3 trials, DERBY and OAKS.  We will await the results of this trial over the next few years.


Next we heard from Dr. Kashani regarding the his work on stem cells for geographic atrophy, a topic that has been popular in the media recently. Human embryonic stem cells have been bioengineered to create a subretinal RPE patch for the treatment of GA.  Dr. Kashani showed us a stimulating surgical video demonstrating the process of implantation of this patch. The results of 5 patients in the trial were discussed, one of which had an improvement in visual acuity, and 2 with improved fixation.


Dr. Kuriyan then took the stage to caution us of “direct to consumer” marketing being utilized by “cell therapy” clinics. These clinics have been taking advantage of the recent increased interest in stem cell therapy to administer treatment in various forms, from intravenous, retrobulbar, to intravitreal injections. They claim to treat a variety of conditions including wet macular degeneration, retinitis pigmentosa, and even “ophthalmology.”  As retina specialists, we should strongly advise our patients against receiving care from these entities due to the risk of devastating complications.


Lastly, Dr. Lad redirected our attention to those patients with earlier phases of macular degeneration, in whom visual acuity is preserved, but who are still symptomatic due to the compromise of other visual functions, such as contrast sensitivity.  Various exams such as cone contrast test, microperimetry, and particularly low luminance deficit testing can better demonstrate the shortcomings patients experience on a daily basis.

Overall, the morning session provided stimulating and relevant information for all retina specialists, and we look forward to hearing more.