Pathogenesis of AMD
Genetic factors felt to be contributory to the development of AMD were discussed. The authors paid particular attention to the recent finding of the role that a mutation in the complement factor H gene plays in the etiology of AMD. These findings will undoubtedly serve as the foundation for future therapeutic interventions.
Pharmacotherapy of AMD
The pharmacokinetics of intravitreal bevacizumab (Avastin, Genentech) were reviewed as well as various intravitreal anti-VEGF treatment regimens (dose, dosing frequency) were reviewed. Most of this discussion revolved around treatment with intravitreal bevacizumab or ranibizumab (Lucentis, Genentech), with less discussion surrounding pegaptanib (Macugen, OSI Eyetech). The case was made that monthly dosing with ranibizumab is the dosing regimen with the highest level of evidence with the best visual results. However, most ophthalmologists find this approach to be impractical in our ever increasing patient population. Alternative dosing regimens using either an as-needed or PRONTO-style treatment regimen were also considered. Other treatment dosing regimens include a treat-and-extend regimen whereby the patient is treated until “dry” then treated one more time and brought back at increasingly greater evaluation intervals and then retreated when signs of recurrent CNV activity are seen. There seems to be no consensus opinion as to what is the best and most practical approach (Avastin or Lucentis, monthly dosing vs as-needed dosing). It seems that there is a 50:50 split between Avastin and Lucentis usage amongst retinal surgeons, with most opting for some form of as-needed therapy. Everyone is eagerly anticipating the results of the CATT trial comparing Avastin with Lucentis and monthly dosing with as-needed dosing. The economic impact of expensive pharmacotherapies was also discussed in both the macro- and micro-economic context. Of the top 40 most expensive codes in all of medicine (as reported by CMS), Avastin usage was number 2 (includes oncologic usage). Reimbursement problems with Lucentis was discussed, but hopefully this will be helped with the introduction of the new J code recently introduced this week for Lucentis (J2778).
Combination therapy for AMD
To try to reduce the frequency and/or improve the efficacy of anti-VEGF therapy, different adjunctive treatment regimens to anti-VEGF monotherapy were reviewed. Most combination regimens discussed included verterporfin (Visudyne, QLT) photodynamic therapy with or without intravitreal dexamethasone and Avastin or Lucentis. Early data was presented, but the consensus is that it is too soon to tell if these combination approaches have any additional benefit over either Lucentis or Avastin monotherapy alone.
Future therapies of AMD
There are over a hundred open and recruiting clinical trials for the treatment of AMD, a literal explosion of research in the last 2-3 years. There is growing interest in the treatment of atrophic retinal diseases such as dry AMD with geographic atrophy and retinitis pigmentosa. Some of these therapies include topical administration of pharmacotherapeutics and sustained release intravitreal implants.
Surgical Instrumentation, Techniques, and Surgical Adjuvants
Most of the discussion here surrounded the choice of vitrectomy instrumentation size: 20g, 23,g or 25g and the use of surgical adjuvants (staining agents). The introduction of new valved trocars by DORC has heralded the introduction a true “closed vitrectomy” system. In addition, much attention was paid to “duty cycle.” Duty cycle is the proportion of the time that the vitrectomy port is open. A closed port does not aspirate much vitreous, after all, so the greater proportion of the time that the vitrectomy port is open, the better fluidics the surgeon will appreciate. As it turns out, size does matter. The smaller gauge vitrectomy probes tend to have more advantageous flow rates and duty cycles compared with conventional 20g vitrectomy probes. This is true especially as the cut rate increases. That is to say that 23 and 25g systems maintain advantageous duty cycles as the cut rate increases. 20g systems, by contrast, appreciate a decreased duty cycle as the cut rate increases. This was shown elegantly using high-speed photography by Kirk Packo of Rush University Medical College and separately by Mark Humayun from the Doheny Eye Institute at USC.
Vitreoretinal Surgery
Mittra and colleagues have demonstrated that long-acting gas tamponade (C3F8) with extended face-down positioning (more than 1 week) may not be necessary in order to achieve anatomical and visual success following macular hole repair. Using SF6 and only 1 to 2 days of face-down positioning, excellent anatomic and visual results were realized. Treatment approaches to patients with pathologic (high) myopia was also discussed, especially with regard to myopic macular schisis (also known as myopic traction maculopathy). Dr. Pannozzo shared his data, which showed that vitrectomy with ILM peeling using ICG staining was effective for reducing the epiretinal macular traction, although often times there is a delayed recovery in vision months after the surgery. Unlike other studies on this condition, he found that not using intraocular gas tamponade still led to favorable anatomic and visual results.
Late Breaking Topics-1
In a retrospective multicenter study by Martidis and co-workers, both Avastin and Lucentis monotherapy were found to be separately effective in an interim analysis for the treatment of neovascular AMD.
Dan Martin who is the Principal Invesitgator of the CATT trial (1200 patients, 300 per treatment arm) comparing Avastin with Lucentis (also monotherapy vs as-needed therapy) for the treatment of neovascular AMD reported on the status of this NEI-sponsored and much anticipated trial. He also reviewed the re-treatment criteria for the as-needed treatment groups. He dispelled the myth that the CATT was at risk for funding loss. This is a $50 million study, $16.2 million which comes from the NEI and the balance from usual-care billing. There was an issue with the masking during this trial due to the way the patient is billed for usual-care billing (the patient may see their co-pay amount and be able to deduce which treatment they are receiving). The impact of this shortcoming was downplayed. He also dispelled the myth that Genentech has somehow sabotaged this trial, although they are certainly not supporting the trial. The study is fully funded and ready to begin. An investigator meeting was held in September of 2007. The FDA IND is in place and the recent Genentech compounding pharmacy decision will not have an impact on this study. The first patient will be enrolled in January of 2008.