Before the use of liver transplantation, early-onset ATTRv amyloidosis (before age 50 years) was fatal, with an expected survival of approximately ten years from disease onset.1. Liver transplantation was introduced in the 1990s as the first treatment for ATTRv amyloidosis and persisted for two decades as the only available therapy with clear clinical evidence of benefit. In the last decade, various disease-modifying therapies have been developed. In Japan, the stabilizer TTR (tafamidis [Vyndaqel]; Pfizer, New York, NY, USA) and TTR mRNA silencers (patisiran [Onpattro]; Alnylam, Cambridge, MA, USA) are approved for clinical use24. These drugs, in addition to liver transplantation, can reduce the systemic production of ATTRv and significantly improve survival and quality of life in these patients. However, ocular tissues, the retinal pigment epithelium and the ciliary epithelium, also synthesize ATTRv.25.26, and these drugs do not affect ocular ATTRv production or ocular complications. This continuous production of ATTRv may explain the difficulty in lowering IOP and why the course of glaucoma is accelerated in these patients.8.
Our present study, which provided medium-term follow-up results, indicated that the effect of SLOT ab interna, as well as that of trabeculectomy with MMC, appeared to be restricted to secondary glaucoma associated with ATTRv amyloidosis. The cumulative probability of treatment success in our study was 0.83 at 1 year, 0.63 at 2 years, and 0.22 at 3 and 4 years. We classified ten eyes (56%) of eight patients as surgical failures. In our previous results of trabeculectomy with MMC for patients with ATTRv Val30Met, the cumulative survival values were 0.88 at 1 year, 0.81 at 2 years, 0.63 at 3 years, and 0.17 at 4 years. We classified 8 (50%) of 16 eyes as surgical failures14. In both studies, approximately half of the eyes required additional surgical procedures within two years of surgery.
Although a trabecular directed MIGS, such as SLOT ab interna in this study, can alleviate outflow resistance in the trabecular meshwork, 25-50% of the total outflow resistance is still in the trabecular meshwork. conventional outlet distal to Schlemm’s canal.27. Therefore, effective function of the distal outflow tract is very important to reduce IOP after MIGS. Given the pathophysiology of secondary glaucoma associated with ATTRv amyloidosis, amyloid deposition in the trabecular meshwork would play a predominant role. Therefore, a trabecular-targeted MIGS that removes the affected trabecular meshwork seemed a logical strategy. However, our insufficient results suggested that continuous amyloid deposition in the distal outflow tract and/or perivascular amyloid deposition in episcleral tissues may result in IOP increases even after SLOT ab interna. Barbosa et al.28 described a successful case report using Kahook Dual Blade excisional goniotomy in a patient with ATTRv amyloidosis, but the follow-up period was only 6 months.
In the present study, ten eyes (56%) of eight patients required additional surgery to lower IOP. We performed SLOT ab interna as a first additional surgery, because SLOT ab interna is less invasive than other surgeries and requires a short operating time, and we hoped that this procedure might allow removal of a slight amyloid deposition around the trabeculotomy slit. or the collector channels, if necessary. existed, which can lower IOP. Although VGA was needed within one year after additional internal SLOT ab in five of seven eyes, IOPs remained stable in the other two eyes. In both eyes, an additional SLOT could remove amyloid deposition in the distal outflow tract, especially around the trabeculotomy slit or collecting canals. No serious complications related to the additional SLOT ab interna procedures were observed.
In the past decade, two different types of long-tube glaucoma drainage devices for refractory glaucoma have been approved in Japan: the Baerveldt Glaucoma Implant (BGI; Abbott Medical Optics, Abbott Park, IL, USA) in 2012 and the AGV in 2014 Recently, Kakihara et al.29 suggested that BGI surgery may now be the optimal treatment for secondary glaucoma in Japanese patients with ATTRv amyloidosis, as it produced good results in five eyes of four patients with a mean follow-up of 4.4 years. Martha et al.30 also showed that VGA implantation is a safe and effective option in secondary glaucoma in Portuguese patients, with excellent success and low complication rates in 114 eyes of 87 patients with a mean follow-up of 3.8 years. In that report, Marta et al. stated that although they did not publish data on the effects of trabeculectomy in these glaucoma patients, their experience up to 2009 indicated that trabeculectomy was not a good option, because the success rate was quite low. They reported a better cumulative probability of VGA treatment success with rates of 0.98 at 1 year, 0.97 at 2 years, 0.95 years at 3 years, and 0.89 at 4 years. They also suggested that VGA may be superior to filtering surgery, possibly because these patients had a fragile and modified conjunctiva, as well as associated amyloid deposition, previous surgeries, and the cumulative use of multiple eye drops (not just for glaucoma but also for dryness). eye). In our study, we implanted the VGA after SLOT ab interna in seven eyes, and IOPs were controlled to <21 mmHg at the final visit in all but one eye (detailed data not shown). We also performed MP-TSCPC in eyes that received prior incisional glaucoma surgery, such as SLOT ab interna and AGV, after consultation with patients. Given the above results, long tube glaucoma surgeries appear to be preferable for secondary glaucoma associated with ATTRv patients. However, SLOT ab interna and any type of trabecular-directed MIGS, which are safer and less invasive procedures, can be used before long-tube glaucoma surgeries for young or hesitant patients for long-tube surgeries, especially with a careful explanation of poor long-term results. effect.
In the present study, we used a 360° incision in Schlemm’s canal in 15 eyes (83%) and a 180° incision in three eyes (17%). We chose the SLOT ab interna for our patients because we thought it reasonable to hypothesize that IOP reduction would be proportional to the extent of the diseased trabecular meshwork and the SLOT ab interna procedure wishes to make a longer incision than is used in various types of trabecular meshwork. Trabecular targeted MIGS, including trabecular ablation via Trabectome, iStent, Kahook Dual Blade, and internal ab microhook trabeculotomy. Although the most appropriate length of Schlemm’s canal incisions is still controversial, we recently reported that different lengths and locations of Schlemm’s canal incisions during internal ab SLOT for open-angle glaucoma, including a 360° incision, a 180° upper incision and a 180° lower incision did not affect either IOP reduction or medication requirements during a 12-month follow-up.23 Therefore, we currently use the 180° incision in Schlemm’s canal for the initial surgery; in this study, we used this incision in three recent cases.
Our study has several limitations that must be taken into account when interpreting its results. The main limitations are its retrospective design, the lack of a control group, and the inclusion of eyes with previous eye surgeries. Confounding factors and bias are inherent in retrospective studies. To minimize these limitations, we will need to conduct a multicenter study and select strict inclusion and exclusion criteria. The inclusion of both eyes of a patient and various follow-up periods may also have introduced bias, although we minimized this by using a mixed-effects regression model. Although this disease is rare and the number of patients is small in this single-center study, further studies with larger cohorts and longer follow-up using SLOT ab interna or other trabecular-targeting MIGS devices are warranted.
In summary, as a consequence of the significant improvement in survival of patients with ATTRv amyloidosis, glaucoma is becoming a more frequent serious complication. Our results suggest that SLOT ab interna, as well as trabeculectomy with MMC, may not have a sufficient long-term effect on secondary glaucoma resulting from ATTRv amyloidosis.