Interventional procedure overview of nerve graft for corneal denervation

Corneal sensation

In a before-and-after study of 16 people (14 aged 18 or under), there was a statistically significant increase in central corneal sensation. It increased from a mean of 0.8 mm (SD 2.5 mm) before surgery to 49.7 mm (standard deviation [SD] 15.5 mm) at a mean follow up of 24.0 months (p<0.0001; Capatano, 2019).

In a non-randomised controlled trial of 10 people, there was a statistically significant increase in corneal sensation. It increased from 2.5 mm (SD 5.4 mm) before surgery to 22.5 mm (SD 18.3 mm) after 1‑year follow up (p=0.002). In the comparator group, 16 people had direct neurotisation. At 3 and 6 months follow up, people who had direct neurotisation had a statistically significantly higher change from baseline corneal sensation than people who had indirect neurotisation (p=0.042 and p=0.048, respectively). However, this difference was not seen at 1‑year follow up (p=0.579; Fogagnolo, 2020).

In a case series of 11 people, corneal sensation improved in 9 people and did not change in 2 people at a mean follow up of 14.5 months. There was no statistical analysis done (Elalfy, 2021).

In a case series of 6 people, corneal sensation was regained in all people at a final follow up of 6 to 17 months. There was no statistical analysis done (Weis, 2018).

Visual acuity

In the before-and-after study of 16 people (14 aged 18 or under), there was no statistically significant change in BCVA before and after surgery. The authors note that this is 'due to the presence of corneal stromal scarring in all the eyes in our cohort' (Capatano, 2019).

In the non-randomised controlled trial of 10 people, there was no statistically significant change in decimal BCVA from 0.42 (SD 0.23) before surgery to 0.48 (SD 0.27) at 1‑year follow up (p=0.054). This study reported decimal BCVA in which higher scores indicate better visual acuity. In the comparator group, 16 people had direct neurotisation. There was no statistically significant difference in the improvement of BCVA between the 2 techniques (p=0.089; Fogagnolo, 2020).

In the case series of 11 people, visual acuity improved in 6 people, stabilised in 3 people, and deteriorated in 2 people at a mean follow up of 14.5 months. There was no statistical analysis done (Elalfy, 2021).

In the case series of 6 people, 5 people had improved visual acuity after neurotisation. There was no statistical analysis done (Weis, 2018).

Corneal damage

In the before-and-after study of 16 people (14 aged 18 or under), there was a statistically significant decrease in the number of people with persistent epithelial defects from 17 people (89%) before surgery to 4 people (21%) after surgery (p<0.0001; Capatano, 2019).

In the non-randomised controlled trial of 10 people, there was a statistically significant decrease in the area of the epithelial defect from 12.40 mm² before surgery to 0.10 mm² after surgery (p=0.006). In the comparator group, 16 people had direct neurotisation. There was no statistically significant difference in the change in epithelial defect area between the 2 techniques (p=0.120; Fogagnolo, 2020)

In the case series of 11 people, no one developed any further corneal ulcers after the procedure at a mean follow up of 14.5 months. Additionally, there was a decrease in corneal and conjunctival staining in 10 people, and no change in 1 person. There was no statistical analysis done (Elalfy, 2021).

In the case series of 6 people, 4 people had improved corneal epithelial status after neurotisation. There was no statistical analysis done (Weis, 2018).

Corneal reinnervation

In the case series of 11 people, in 4 of 5 people assessed, nerve fibre density, nerve branch density, nerve fibre length, and total branch density generally increased over a mean follow up of 14.5 months. There was no statistical analysis done (Elalfy, 2021).

In the non-randomised controlled trial of 25 people, there was an increase in the mean corneal nerve fibre length from 1.8 mm/mm² (SD 0.15 mm/mm²) before surgery to 14.67 mm/mm² (SD 7.92 mm/mm²) at 1‑year follow up. Data was not provided separately for the indirect and direct neurotisation groups. However, the change in corneal nerve fibre length from before to after surgery did not differ significantly between the groups (p=0.833; Fogagnolo, 2020)

Tear outcomes

In the case series of 11 people, the following tear outcomes were reported at a mean follow up of 14.5 months. No statistical analysis was done (Elalfy, 2021):

Use of conservative treatments

In the case series of 11 people, reduction in lubricant use after surgery was reported by 3 people, with 8 people reporting no change. No statistical analysis was done (Elalfy, 2021).

Quality-of-life outcomes

In the case series of 11 people, 6 people completed the before and after surgery NEI VFQ‑25. In general, there were improvements in overall vision, ocular discomfort, and reading, and a reduction in limitation of activities and psychosocial impact of the disease. No statistical analysis was done (Elalfy, 2021).

Corneal sensation

In a case series of 2 people, corneal sensation improved from absent to 47 mm in 1 person over 8 months follow up, and from between 0 and 15 mm to 37 mm in 1 person over 5.5 months follow up. There was no statistical analysis done (Jowett, 2019).

Visual acuity

In the case series of 2 people, visual acuity improved from 20/125 to 20/80 in 1 person over 4.5 months follow up, and from 20/300 to 20/80 in 1 person over 5.5 months follow up. There was no statistical analysis done (Jowett, 2019).

Corneal sensation

In a case report of 1 person, corneal sensation improved from absent before surgery to 10 mm at 12 months follow up (Benkhatar, 2018).

Visual acuity

In the case report of 1 person, BCVA did not change from below 20/200 before surgery to below 20/200 at 6 months follow up (Benkhatar, 2018).

Corneal appearance

In the case report of 1 person, corneal appearance did not improve after surgery (Benkhatar, 2018).

Corneal reinnervation

In the case report of 1 person, there was an absence of corneal nerve fibres before surgery. At 6 months after surgery, nerve fibres were present at high density in both nasal and temporal sectors (Benkhatar, 2018).

Corneal sensation

In a case report of 1 person, corneal sensation improved from absent before surgery to 40 mm at 12 months follow up (Bourcier, 2019).

Visual acuity

In the case report of 1 person, BCVA improved from 20/200 before surgery to 20/80 at 12 months follow up (Bourcier, 2019).

Corneal sensation

In a before-and-after study of 17 people, there was a statistically significant increase in mean corneal sensation from 3.6 mm (SD 8.4 mm) before surgery to 44.2 mm (SD 16.2 mm) after surgery (p<0.01). The mean final follow up in this study was 17.7 months. However, the follow up time for the assessment of corneal sensation is not clearly described. There were no statistically significant differences in time to first gain of corneal sensation, time of maximum gain of corneal sensation, or before-after surgery improvement in corneal sensation when comparing end-to-end with end-to-side coaptation, supraorbital with infraorbital donor nerves, and ipsilateral with contralateral donor nerves (Sweeney, 2020).

In a case series of 7 people, all had improved corneal sensation after surgery. Follow up ranged from 3 to 10 months. There was no statistical analysis done (Leyngold, 2019).

Visual acuity

In the before-and-after study of 17 people, there was no statistically significant change in BCVA from 20/500 before surgery to 20/300 after surgery (p=0.22; BCVA measurements were converted into LogMAR for analysis). The mean final follow up in this study was 17.7 months. However, the follow up time for the assessment of visual acuity is not clearly described. The authors state that visual acuity gains were limited by pre-existing conditions (Sweeney, 2020).

In the case series of 7 people, 6 of 7 had improved BCVA after surgery. Follow up ranged from 3 to 10 months. There was no statistical analysis done (Leyngold, 2019).

Corneal damage

In the case series of 7 people, of the 5 people who had an epithelial defect before surgery, all were resolved after surgery. Follow up ranged from 3 to 10 months. There was no statistical analysis done (Leyngold, 2019).