Functional and Structural Changes Following Corneal Neurotisation in the Management of Neurotrophic Keratopathy: UK Single Centre Series

Figures & data

Table 1 Patient Demographics, Characteristics and Aetiology of Neurotrophic Keratopathy (NK)

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8	Patient 9	Patient 10	Patient 11
Sex/Age	F/40	M/28	F/46	M/61	F/60	M/43	F/38	F/62	F/51	F/25	F/38
Eye	Left	Left	Left	Left	Left	Left	Right	Left	Left	Left	Right
Aetiology	Posterior fossa infarction	Traumatic multiple cranial nerve palsy	Vestibular Schwannoma	Traumatic multiple cranial nerve palsy	Ethmoidal carcinoma and craniofacial Resection	Cerebral vascular accident	Vestibular schwannoma	Vestibular schwannoma	Polyneuropathy due to chemo-therapy	Herpes simplex keratitis	Trigeminal schwannoma
Surgery	Jan 2016	Feb 2016	Jun 2016	Jan 2017	May 2017	Jun 2017	Jul 2017	Sep 2017	Nov 2017	Feb 2018	Apr 2018
Surgical approach	Supraorbital (end to end)	Supraorbital+supratrochlear(end to end)	Supratrochlear (end to end)	Supraorbital+supratrochlear(end to end)	Supraorbital+supratrochlear(end to end)	Supraorbital (end to end)	Supraorbital (end to end)	Supratrochlear (end to end)	Supratrochlear (end to end) +AMT	Supraorbital (end to end) +AMT	Supraorbital+supratrochlear (end to end) +AMT
Follow-up	18 months	36 months	12 months	18 months	9 months	15 months	9 months	12–24 months	9 months	4 months	8 months

Figure 1 Preoperative neurotrophic keratopathy demonstrated by scarring and punctate keratopathy with improvement in corneal sensations and clear cornea in patient 6.

Table 2 Functional Outcome Data of Patients with Neurotrophic Keratopathy

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8	Patient 9	Patient 10	Patient 11
Vision (Snellen)	6/12 → 6/18	6/36 → 6/18	6/30 → 6/15	CF → 4/60	6/15→6/15	6/36 → 6/24	6/12 → 6/7.5	6/15 → 6/9	6/12 → 6/24	6/6→ 6/6	6/7.5→ 6/7.5
Corneal Staining (Oxford grade)	III → I	IV→ I	III→ 0	III → I	II → I	II → I	II → II	II→ I	II → 0	II → I	I → 0
TFBT (sec)	3 → 5	5 → 8	4 → 7	2 → 5	1 → 4	3 → 4	8 → 4	4 → 10	1 → 5	1 → 3	2 → 10
TMH (mm)	0.2 → 0.8	0.8 → 1.5	0.5 → 1	0.5 →0.5	0.5 → 0.6	0.5 → 1	0.1 → 0.6	0.5 →0.5	0.6 →0.6	0.2 →0.2	1 → 2
Schirmer (mm)	14 → 14	7 → 18	10 → 14	5 → 5	12 → 12	8 → 18	10 → 10	12 → 12	5 → 5	15 → 24	10 → 10
Tear Osmolarity (mOsmol/L)	279 → 281	276 → 277	278 → 267	289 → 276	292 → 208	288 → 288	306 → 291	374 → 323	276 → 276	328 → 315	299 → 293
Pachymetry (micrometer)	462 → 520	360 → 448	553 → 543	456 → 466	553 → 560	540 → 557	501 → 526	557 → 596	521 → 529	499 → 499	523 → 527
Cochet–Bonnet Corneal Sensation (mm)	0 →10	0 →60	0 →10	0 →0	0 →50	0 →10	0 →0	0 →10	0 →30	0 →50	0 →10

Abbreviations: AMT, amniotic membrane; CF, counting fingers; F, female; M, male; TFBT, tear film break-up time; TMH, tear meniscus height.

Figure 2 In vivo confocal microscopy images of the subbasal nerve plexus for patient 7 taken at 50µm depth- Pre op presence of one main nerve fibre (arrow) (A); one main nerve fibre (arrow) and nerve branches (dotted arrow) at 3 month (B); one main nerve fibre (arrow) and multiple nerve branches (dotted arrow) at 6 month (C); three main nerve fibres and multiple nerve branches at 12 month (D) after corneal neurotisation surgery (-: main nerve, –: nerve branches showing nerve regeneration).

Table 3 Nerve Parameters of Five Patients with IVCM Data

Subject	Mean Corneal Nerve Parameters and Duration Post-Surgery
	Preop				3 Months				6 Months				12 Months
	NFD	NBD	NFL	TBD	NFD	NBD	NFL	TBD	NFD	NBD	NFL	TBD	NFD	NBD	NFL	TBD
Patient 2	0 (0)	0 (0)	0 (0)	0 (0)	4.1 (2.9)	10.4 (7.8)	4.9 (1.2)	20.8 (7.8)	4.7 (8.1)	6.3 (10.8))	7.6 (2.8)	20.3 (20.9)	3.1 (3.1)	4.7 (8.1)	8.1 (2.1)	21.9 (16.8)
Patient 3	0 (0)	0 (0)	0.2 (0.3)	0 (0)	0 (0)	0 (0)	3.4 (0.4)	3.1 (5.4)	4.7 (2.7)	7.8 (8.1)	6.5 (1.1)	21.8 (13.6)	6.2 (0.1)	1.6 (2.7)	6.5 (0.9)	15.6 (14.3)
Patient 4	0 (0)	0 (0)	0.9 (0.8)	3.1 (3.1)	0 (0)	0 (0)	3.1 (0.5)	3.1 (2.1)	1.6 (2.7)	0 (0)	3.1 (1.4)	3.1 (3.1)	0 (0)	0 (0)	4.3 (0.6)	10.9 (9.2)
Patient 5	7.8 (2.8)	26.5 (19.4)	8.6 (1.5)	42.1 (17.4)	1.6 (2.7)	0 (0)	5.1 (1.9)	7.8 (6.8)	0 (0)	0 (0)	4.9 (1.6)	21.8 (6.9)	NA	NA	NA	NA
Patient 7	9.4 (3.2)	0 (0)	4.7 (0.8)	3.1 (5.4)	20.3 (9.2)	4.7 (5.2)	12.8 (1.6)	18.7 (4.4)	6.2 (0)	18.7 (8.8)	11.2 (1.5)	56.2 (25.4)	19.9 (4.2)	19.2 (4.5)	11.6 (3.1)	58.3 (4.5)

Note: Values in parenthesis = standard deviation.

Abbreviations: NFD, nerve fibre density in number of fibers/mm²; NBD, nerve branch density in number of branches/mm²; NFL, nerve fibre length in mm/mm²; TBD, total branch density per mm².

Table 4 Nerve Parameters (Mean Change of Nerve Parameters) for the Five Patients at Different Postperative Time Points

	3 Months				6 Months				12 Months
	NFD	NBD	NFL	TBD	NFD	NBD	NFL	TBD	NFD	NBD	NFL	TBD
Patient 2	4.1	10.4	4.9	20.8	4.7	6.3	7.6	20.3	3.1	4.7	8.1	21.9
Patient 3	0	0	3.2	3.1	4.7	7.8	6.3	21.8	6.2	1.6	6.3	15.6
Patient 4	0	0	2.2	0	1.6	0	2.2	0	0	0	3.4	7.8
Patient 5	−6.2	−26.5	−3.5	−34.3	−7.8	−26.5	−3.7	−20.3	NA	NA	NA	NA
Patient 7	10.9	4.7	8.1	15.6	−3.2	18.7	6.5	53.1	10.5	19.2	6.9	55.2

Abbreviations: NFD, nerve fibre density per mm²; NBD, nerve branch density per mm²; NFL, nerve fibre length in mm/mm²; TBD, total branch density per mm²; NA, not available.

Figure 3 Nerve parameters (nerve fiber density, nerve fiber length, nerve branch density and total branch density) in patients 2, 3, 4, 5 and 7 improving from preoperative to early (3 month), intermediate (6 months) and late (12 months) postoperative follow-up.