Semiautomated and Automated Quantitative Analysis of Corneal Sub-Basal Nerves in Patients With DED With Ocular Pain Using IVCM

Abstract

PurposeInvestigate the correlation and agreement between the results of semiautomated and fully automated quantitative analysis of the corneal sub-basal nerve plexus (SNP) in patients with dry eye disease (DED) with ocular pain using in vivo confocal microscopy (IVCM).MethodA total of 50 voluntary participants were enrolled in this study, i.e., 25 DED patients with ocular pain and 25 healthy controls. Each patient underwent an evaluation of ocular symptoms that utilized: the Ocular Surface Disease Index (OSDI), the Ocular Pain Assessment Survey (OPAS), the tear film breakup time (TBUT) test, the Schirmer test, corneal staining, and IVCM. Five SNP images of the cornea of each eye were selected and analyzed using a semiautomated analysis software (NeuronJ) and a fully automated method (ACCMetrics) to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL).ResultsThe intraclass correlation coefficient (ICC) of the CNFD (0.460 [0.382–0.532], p < 0.001), CNBD (0.608 [0.545–0.665], p < 0.001), and CNFL (0.851 [0.822–0.875], p < 0.001) represents the repeatability and consistency of measurements by the NeuronJ and ACCMetrics software. The CNFL values (r = 0.881, p < 0.001) obtained using the two methods have extremely high correlation, and similarly, the CNFD values (r = 0.669, p < 0.001) and CNBD values (r = 0.703, p < 0.001) are highly correlated. The CNFL had the biggest area under the curve (AUC; 0.747 [0.700–0.793], p < 0.001) when using ACCMetrics. In DED patients with ocular pain, the mean CNFD values for semiautomated and fully automated quantization were 23.5 ± 8.1 and 23.8 ± 8.6 n/mm2; the mean CNBD values were 46.0 ± 21.3, 35.7 ± 23.3 n/mm2; and the mean CNFL values were 19.3 ± 4.3 and 15.2 ± 3.8 mm/mm2, which were significantly lower than healthy subjects (p < 0.001).ConclusionThere is a significant correlation between the measurements obtained via ACCMetrics and NeuronJ, especially for CNFL, which can be considered as the primary indicator in the diagnosis of DED with ocular pain. The SNP of the disease was significantly lower than that of healthy subjects.

The impact of dry eye disease on corneal nerve parameters: A systematic review and meta‐analysis

“…Of the 22 included studies, a majority were observational studies including 17 cross-sectional controlled studies [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and four retrospective case-control studies. [36][37][38][39] Comparisons between DED groups and healthy controls at baseline were undertaken in one randomised controlled trial.…”

“…All included studies mentioned the diagnosis of DED using a combination of symptoms and signs. Ten studies outlined diagnostic methods without reference to published criteria, 20,22,24,27,31,34,36,37,39,40 while seven referred to the TFOS DEWS II, 19,23,25,26,29,30,33 three referred to TFOS DEWS I, 28,32,38 one referred to the 2005 Japanese Dry Eye diagnostic criteria 21 and one referred to the 2013 Chinese Clinical Diagnosis and Treatment Experts Consensus of Dry Eye. 35 Further details on the diagnostic methods are outlined in Table S5.…”

“…The degree of twistedness of nerves which could be classified according to a subjective grading system or custom aggregate measure the location of the cornea imaged, all of them included the central cornea, [19][20][21]23,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] with three studies also imaging additional locations: one included the lower third of the cornea, 21 one included mid-peripheral locations (approximately 5 mm in diameter including the central cornea) 19 and one imaged the upper, lower, nasal and temporal cornea. 34 The number of outcome assessors involved in analysing the images obtained were specified in 17 studies: seven studies involved one outcome assessor, 23,26,28,[30][31][32]38 10 studies involved two outcome assessors, 19,21,22,27,33,34,36,37,39,40 while the remaining five studies did not specify the number of outcome assessors involved. 20,24,25,29,…”

Long-Term Clinical Outcome of Low-Temperature Plasma Ablation Treatment for Recurrent Corneal Erosions

“…During our follow-up, we found a slight increase in the degree of dry eyes (NIKTMH decreased from 0.210 ± 0.054 mm to 0.208 ± 0.045 mm, TBUT decreased from 6.191 ± 2.811 s to 5.815 ± 2.802 s), which may be because of the injury of the corneal subbasal nerves caused by the corneal ablation, which has been reported in many studies to be associated with dry eye disease [ 31 , 42 ]. One complication we observed was an exacerbation of postoperative astigmatism (from 1.5 D to 8.3 D) due to intraoperative manipulation problems, which recovered 6 months later.…”

“…Patients were scheduled for follow-up visits preoperatively, 1, 3, 6 and 12 months postoperatively, and lastly before the end of our study. The main assessments included a subjective symptom questionnaire, intraocular pressure, slit lamp biometric microscopy, corneal fluorescein staining, dry eye examination, in vivo confocal corneal microscopy (IVCM, HRT-3, Heidelberg Engineering GmbH, Heidelberg, Germany) [ 31 ] and corneal topography. The main outcomes included recurrence after treatment, pain scores (visual analogue scale, VAS), tear film breakup time (TBUT), non-invasive keratograph tear meniscus height (NIKTMH), corneal nerve fiber length (CNFL), corneal astigmatism, corneal thickness, IVCM image changes and postoperative complications.…”