Gly83Arg mutation tied to eye condition’s recurrence after surgery
Rates of glaucoma similar to what's been reported with Val30Met variant
A mutation of the TTR gene that’s been exclusively reported in Chinese people causes an eye condition called vitreous opacity that can be successfully managed with eye surgery, but eventually recurs in nearly all cases after a mean of five years, a study shows.
After surgery, which is called a vitrectomy, the rates of glaucoma, where fluid builds up in the eye, were high with the Gly103Arg mutation, not unlike what’s been reported for people carrying Val30Met, the most common TTR mutation causing familial amyloid polyneuropathy.
“Inevitable [disease] recurrence and post-vitrectomy glaucoma pose challenges to the treatment of” Gly103Arg-related disease, which is associated with a FAP-like profile marked by eye and neurological involvement, the researchers wrote. “Delaying vitrectomy appropriately and maintaining regular follow-up visits is advisable.”
The study, “Hereditary vitreoretinal amyloidosis with transthyretin Gly83Arg variant,” was published in Eye.
Hereditary transthyretin amyloidosis, or hATTR, is a group of conditions caused by TTR gene mutations that lead to a faulty transthyretin (TTR) protein being produced that forms clumps called amyloid fibrils that deposit in tissues and cause damage. FAP is a type of hATTR where amyloid fibrils accumulate mainly in the nerves outside the brain and spinal cord, but can build up in the eyes and heart too.
The Gly103Arg mutation is mainly associated with eye problems, particularly vitreous opacity, where the gel-like substance that fills most of the eye, called the vitreous, begins to shrink, forming strands that appear in the visual field as floaters. Other symptoms, including those related to nerve damage, are usually mild and may develop years after the onset of eye problems.
“Vitrectomy is an effective treatment for vitreous amyloidosis,” wrote the researchers, who noted, however, that evidence suggests that disease recurrence after surgery and the development of secondary glaucoma may continue to affect vision in these patients.
A look at long-term effects of vitreous opacity
Here, researchers in China retrospectively analyzed up to 15 years of data from 14 adults (seven men, seven women) from the same family who had Gly83Arg-related hATTR to obtain some long-term follow-up data on vitreous opacity associated with the Gly103Arg mutation.
All complained of floating objects and reduced vision as their initial symptoms, suggestive of vitreous opacities, which occurred at a mean age of 40.9 (range, 29-52).
At their diagnosis, none of the patients showed signs of disease involvement in other tissues. Four patients developed nerve damage symptoms that included numbness and muscle weakness between five and 21 years later, however.
A vitrectomy was performed on 23 eyes from 13 patients. The surgery involves removing some or all of the vitreous gel and replacing it with another solution. The procedure significantly improved the patients’ vision.
Twenty eyes were followed up after surgery for a mean of more than 7.5 years and up to 13.5 years. All but two of those eyes (90%) showed a recurrence of vitreous amyloidosis. This occurred after a mean of nearly five years, and as early as two years after surgery.
During follow-up, another vitrectomy had been performed within five to 12 years after the first surgery in about 44.4% of the eyes where amyloidosis recurred. Also, at 7.5 years after the first vitrectomy, “the cumulative recurrence rate was 94.7%,” the researchers wrote.
Also, 36.4% of the 23 eyes that received a vitrectomy developed glaucoma at a mean of about seven years after surgery (range, two years to nearly 13 years), while none of the five eyes that didn’t undergo surgery developed glaucoma. The high pressure in the eye that marks this condition can lead to damage and blindness.
The difference in glaucoma rates between these two groups was statistically significant, suggesting “the glaucoma in patients with hereditary [Gly83Arg] amyloidosis seems to be associated with vitrectomy,” wrote the researchers, who noted high rates of post-vitrectomy glaucoma (up to 56.1%) have also been reported in people carrying Val30Met, the most common FAP-causing mutation.
Half of the eyes with post-vitrectomy glaucoma received surgery to reduce eye pressure, but this failed to appropriately control it.
“Poor [eye] pressure control in [seven] eyes resulted in severe visual impairment,” wrote the researchers, who recommended delaying vitrectomy until vision loss has a major effect on daily life to minimize recurrence risks and post-surgical complications.
Regular ophthalmic follow-ups, glaucoma monitoring, and treatments to manage eye pressure “should be carried out during the follow-up after vitrectomy to avoid irreversible visual impairment caused by complications,” they wrote.
