Objective Analysis of Corneal Nerves and Dendritic Cells. / Objektive Analyse von Hornhautnerven und dendritischen Zellen.

Corneal nerves and dendritic cells are increasingly being visualised to serve as clinical parameters in the diagnosis of ocular surface diseases using intravital confocal microscopy. In this review, different methods of image analysis are presented. The use of deep learning algorithms, which enable automated pattern recognition, is explained in detail using our own developments and compared with other established methods.

Corneal innervation changes in Alzheimer's: implications for sensory dysfunction.

PURPOSE: To compare, between Alzheimer's disease (AD) patients and healthy individuals, corneal subbasal nerve plexus (CSNP) parameters and corneal sensitivities. METHODS: Twenty-two patients who were followed up with Alzheimer's disease (Alzheimer's group) and 18 age- and gender-matched healthy individuals (control group) were included in this cross-sectional study. CSNP parameters, including nerve fiber length (NFL), nerve fiber density (NFD), and nerve branch density (NBD), were evaluated using in vivo confocal microscopy. Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer. The results were compared between the two groups. RESULTS: In the Alzheimer's group, NFL was 12.2 (2.4) mm/mm2, NFD was 12.5 [3.1] fibers/mm2, and NBD was 29.7 [9.37] branches/mm2. In the control group, NFL was 16.5 (2.0) mm/mm2, NFD was 25.0 [3.13] fibers/mm2, and NBD was 37.5 [10.9] branches/mm2. All three parameters were significantly lower in the Alzheimer's group compared to the control group (p < 0.001, p < 0.001, and p = 0.001, respectively). Similarly, corneal sensitivity was significantly lower in the Alzheimer's group (55.0 [5.0] mm) compared to the control group (60.0 [5.0] mm) (p < 0.001). CONCLUSION: We determined that, in AD, corneal sensitivity decreases significantly, in parallel with the decrease in corneal nerves. Changes in the corneal nerve plexus and a decrease in corneal sensitivity may be used in the early diagnosis and follow-up of AD. In addition, ocular surface problems secondary to these changes should also be kept in mind.

The inferocentral whorl region and its directional patterns in the corneal sub-basal nerve plexus: A review.

There has been a growing application of in vivo confocal microscopy (IVCM) in the examination of corneal microstructure, including different corneal layers and corneal nerve fibers in health and in pathological conditions. Corneal nerves forming the sub-basal nerve plexus (SBNP) beneath the corneal basal epithelial cell layer in particular have been intensively researched in health and disease as a marker for corneal neurophysioanatomical and degenerative changes. One intriguing feature in the SBNP that is found inferior to the corneal apex, is a whorl-like pattern (or vortex) of nerves, which represents an anatomical landmark. Evidence has indicated that the architecture of this 'whorl region' is dynamic, changing with time in healthy individuals but also in disease conditions such as in diabetic neuropathy and keratoconus. This review summarizes the known information regarding the characteristics and significance of the whorl region of nerves in the corneal SBNP, as a potential area of high relevance for future disease monitoring and diagnostics.

Examination of Subbasal Nerve Plexus and Central Corneal Stromal Microstructure in Subjects With Congenital Aniridia, Using in Vivo Confocal Laser Scanning Microscopy.

PURPOSE: During life up to 70% of aniridia subjects develop aniridia-associated keratopathy (AAK). AAK is characterized by limbal stem cell insufficiency, impaired corneal epithelial cell differentiation and abnormal cell adhesion, which leads to centripetal spreading vascularization, conjunctivalization, and thickening of the cornea. Our aim was to examine the subbasal nerve plexus and central corneal stromal microstructure in subjects with congenital aniridia, using in vivo confocal laser scanning microscopy CLSM. METHODS: 31 eyes of 18 patients (55.6% males, mean age: 25.22 ± 16.35 years) with congenital aniridia and 46 eyes of 29 healthy subjects (41.4% males, mean age 30 ± 14.82 years) were examined using the Rostock Cornea Module of Heidelberg Retina Tomograph-III. At the subbasal nerve plexus, corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal total branch density (CTBD), and corneal nerve fiber width (CNFW) were analyzed using ACCMetrics software. Keratocyte density in the anterior, middle and posterior stroma was assessed manually. RESULTS: The CNFD (2.02 ± 4.08 vs 13.99 ± 6.34/mm2), CNFL (5.78 ± 2.68 vs 10.56 ± 2.82 mm/mm2) and CTBD (15.08 ± 15.62 vs 27.44 ± 15.05/mm2) were significantly lower in congenital aniridia subjects than in controls (p < 0.001 for all). CNFW was significantly higher in aniridia subjects than in controls (0.03 ± 0.004 vs 0.02 ± 0.003 mm/mm2) (p = 0.003). Keratocyte density was significantly lower in all stromal layers of aniridia subjects than in controls (p < 0.001 for all). Stromal alterations included confluent keratocytes, keratocytes with long extensions and hyperreflective dots between keratocytes in aniridia. CONCLUSIONS: Decrease in CNFD, CNFL, and CTBD, as well as increase in CNFW well refer to the congenital aniridia-associated neuropathy. The decreased keratocyte density and the stromal alterations may be related to an increased cell death in congenital aniridia, nevertheless, stromal changes in different stages of AAK have to be further analyzed in detail.

Anatomic Variations of the Lateral Branch of the Supraorbital Nerve Observed in Endoscopic Forehead Surgery.

Surgeons dissect carefully in the medial third of the supraorbital rim to preserve the supraorbital nerve (SON) during surgical forehead rejuvenation. However, the anatomic variations of SON exit from the frontal bone have been researched in cadaver or imaging studies. In this study, we report a variation in the lateral branch of SON observed in an endoscopic view during forehead lifts. A retrospective review of 462 patients who underwent endoscopy-assisted forehead lifts between January 2013 and April 2020 was performed. Data, including the location, number, and form of the exit point and thickness of SON and its lateral branch variant, were recorded and reviewed intraoperatively, utilizing high-definition endoscopic assistance. Thirty-nine patients and 51 sides were included, and all patients were female, with a mean age of 44.53 (18-75) years. This nerve exited a foramen in the frontal bone ~8.82 ± 2.79 mm lateral to SON and ~1.89 ± 1.34 mm from the supraorbital margin vertically. Observed thickness variations of the lateral branch of SON included 20 small, 25 medium, and 6 large nerves. This study revealed various positional and morphologic variations of the lateral branch of SON in an endoscopic view. Thus, surgeons can be alerted of the anatomic variations of SON and establish careful dissection during procedures. In addition, the findings of this study will be useful in planning nerve blocks, filler injections, and migraine treatments in the supraorbital region.

Sensory Innervation of the Upper Eyelid and Its Implication for Upper Eyelid Surgery.

PURPOSE: Sensory alterations of the upper eyelid skin and eyelashes are frequently encountered after upper eyelid surgery. The objective of this study was to provide information on the exact course and distribution of sensory nerve fibers through the anatomic planes in the upper eyelid. METHODS: Ten formalin-fixed hemifaces were dissected. The nerve branches of the ophthalmic nerve in the upper eyelid were traced in an anterograde fashion. RESULTS: A total of 151 nerve fibers were recorded during dissection. The infratrochlear, supratrochlear, supraorbital, and lacrimal nerve contributed each to both the upper eyelid skin innervation and the upper eyelid rim plexus in different distribution patterns. The mean distance from the eyelid margin at which nerve fibers pierced from preseptal into the orbicularis muscle was 14 ± 1.1 mm for nerve fibers targeting the eyelid dermis and 3.7 ± 1.2 mm for nerve fibers targeting the eyelid rim plexus ( p < 0.001). The mean intraorbicular course of nerve fibers was 3 mm (0-17; standard deviation 4.1). The mean distance from the eyelid margin at which nerve fibers pierced from the orbicularis muscle into the preorbicular plane was 10 ± 1 mm for nerve fibers innervating the eyelid dermis and 1.3 ± 0.8 mm for nerve fibers innervating the eyelid rim plexus ( p < 0.001). The mean distance of the preorbicular course of nerve fibers was 2 mm (0-15; standard deviation 3.6). CONCLUSIONS: Based on the findings, a certain degree of postoperative eyelid skin numbness is inevitable while eyelash innervation may be spared in upper blepharoplasty.

Central Corneal Subbasal Nerve Plexus Abnormalities in Sjögren Disease: A Pilot Study.

PURPOSE: Small-fiber neuropathy (SFN) is known to be associated with Sjögren disease (SjD), and in vivo corneal confocal microscopy can identify features compatible with SFN. Here, we performed a descriptive study to identify features of SFN of the corneal subbasal nerve plexus using in vivo confocal microscopy. METHODS: We recruited 10 participants from the Sjögren's International Collaborative Clinical Alliance (SICCA), 1 new participant (in an effort to expand the SICCA cohort), and 22 healthy controls. All participants underwent slit-lamp examination and in vivo confocal microscopy of the central corneal subbasal nerve plexus centered about the central whorl to create a 30-image montage. Each image was analyzed with automated software (ACCmetrics, Manchester, United Kingdom) to produce 7 nerve metrics. We performed t-tests and age-adjusted regressions to make comparisons of nerve metrics between participants with SjD and healthy controls. RESULTS: Most nerve metrics were significantly lower in participants with SjD compared with healthy controls. The mean corneal nerve fiber density was found to be 3.5 mm/mm 2 in participants with SjD compared with 10.6 mm/mm 2 in healthy controls (95% confidence interval, -8.4 to -0.93; P = 0.02). Within the 11 participants with SjD, 22 eyes were analyzed on confocal microscopy, and 16 of those eyes (from 9 individuals) did not have an identifiable central whorl. Within the 22 healthy controls, 22 eyes (right eye alone) were analyzed on confocal microscopy, and 21 of those eyes had an identifiable central whorl. CONCLUSIONS: SjD exhibits lower corneal nerve metrics compared with healthy controls. These findings suggest that features compatible with SFN can distinguish SjD from healthy controls and may serve as a potential novel biomarker in identifying SjD.

How the Lifting Amount of Endoscopic Brow Lifts Is Influenced by Supraorbital Nerve Tension and Brow Gliding-Layer Mobility.

BACKGROUND: Sensory nerve tension and gliding-layer mobility in the brow may be significant factors affecting postoperative brow level in an endoscopic brow lift, yet they have rarely been studied. METHODS: To investigate the effects of sensory nerve tension and gliding-layer mobility, the following measurements were performed alongside the endoscopic brow lift in 50 fresh cadaveric hemifaces: amount of brow elevation, critical lifting amount (as sensory nerves became tense), laxity of sensory nerve courses, and mobility of brow-gliding layers. The sensory nerve situations in the subperiosteal and subgaleal dissections were also observed. RESULTS: Supraorbital nerve tension limited the cephalic advancement of the forehead flap. The mean elevation of the brow was 5.8 ± 1 mm (range, 3.5 to 8.6 mm). The mean critical lifting amount was 5.3 ± 1.1 mm (range, 4.0 to 7.3 mm). The mean amount of laxity in the supraorbital nerve (the permissible amount of lift) was 4.1 ± 0.9 mm (range, 2.5 to 5.5 mm). The galeal fat pad was responsible for 60% of brow mobility. The sensory nerve was more protected by a subgaleal dissection in the brow and inferior forehead and by a subperiosteal dissection in the middle and upper forehead. CONCLUSIONS: Cephalic movement of the forehead flap is limited by supraorbital nerve tension. The permitted lifting amount varies from 2.5 to 5.5 mm. Gliding-layer mobility in the brow offsets the postoperative amount of cephalic advancement of the forehead flap. Consideration of supraorbital nerve tension and gliding-layer mobility is recommended to obtain an optimal brow level in endoscopic brow lifts.

Investigation of anterior segment structures of the eye in Behçet's disease using in vivo confocal microscopy.

PURPOSE: We sought to investigate alterations in the corneal subbasal nerve plexus and endothelium in patients with Behçet's disease (BD). METHODS: This cross-sectional study included 64 patients with BD and 30 age- and gender-matched healthy control subjects. Those with BD were classified as having ocular or non-ocular disease. All subjects underwent a corneal endothelial and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). The differences among groups were analyzed using the Kruskal-Wallis test followed by Dunn's multiple comparison procedure. RESULTS: The mean age of study participants was 35.7 ± 10.2 years (16-58) in the ocular BD group, 39.6 ± 14.9 years (11-66) in the non-ocular BD group, and 34.1 ± 11.2 years (21-55) in the control group. No statistical significance was found in terms of age (p = 0.259) or sex (p = 0.560) between groups. The mean endothelial cell density determined with IVCM was 2124.9 [Formula: see text] 417.4 cells/mm2 (1811-3275) in the ocular group and 2546 [Formula: see text] 335 cells/mm2 (1798-3280) in the control group (p = 0.000). In the ocular group, the mean density of the subbasal nerve plexus was significantly lower (p = 0.004), and nerve tortuosity was significantly higher (p = 0.002). CONCLUSIONS: Ocular BD could be responsible for changes in the corneal layers, especially endothelial and corneal nerve structures. Nerve density and tortuosity differences could be inflammatory indicators for BD.

In vivo confocal microscopic study of corneal innervation in Sjögren's Syndrome with or without small fiber neuropathy.

PURPOSE: To study changes in the subbasal nerve plexus by In vivo confocal microscopy (IVCM) in Sjögren's Syndrome (SS) with or without associated Small Fiber Neuropathy (SFN), in order to prevent diagnostic delay. METHODS: Seventy-one patients with SS, including 19 with associated SFN, 20 healthy volunteers and 20 patients with Meibomian gland dysfunction (MGD) were included in this retrospective case-control study. IVCM was used to investigate subbasal nerve plexus density and morphology. RESULTS: Corneal sensitivity as evaluated with the Cochet-Bonnet aesthesiometer was significantly reduced in the SS group versus the control group (P = 0.026) and the MGD group (P = 0.037). The number of inflammatory cells was significantly increased in the SS group to 86.2 ± 82.1 cells/mm2 compared to the control group (P < 0.001). The density of the subbasal nerve plexus was significantly reduced to 16.7 ± 6.5 mm/mm2 in the SS group compared to the control group (P < 0.005) and the MGD group (P = 0.042). The tortuosity of the nerves in the SS group was significantly increased compared to the control group (P < 0.001) and the MGD group (P = 0.025). The average number of subbasal nerve plexus neuromas was significantly increased in the SS group compared to the control group (P = 0.001), with a significant increase in the average number of neuromas in SS patients with associated SFN compared to SS patients without SFN (P = 0.008). CONCLUSION: IVCM can be useful to detect corneal nerve changes in SS patients and may allow earlier diagnosis of the disease and to consider new therapeutic approaches.

Diurnal Variation of Corneal Dendritic Cell Density.

Purpose: To measure variation in corneal dendritic cell density, and percentage of mature to total dendritic cells, in healthy individuals during the sleep/wake cycle.Methods: Using in vivo confocal microscopy, images of the subbasal nerve plexus were captured from 19 healthy, noncontact lens wearing participants. The central cornea and inferior whorl were imaged three times (midday, before sleep, upon awakening). Dendritic cell counts from the images were categorized according to perceived maturity (immature vs mature). Dendritic cell density and percentage of mature to total cells were compared between time points.Result: The median and interquartile range (IQR) of total dendritic cell density in the central cornea was 32.0 (7.0-131.3) cells/mm2 at midday, 37.1 (8.2-103.9) cells/mm2 before sleep, and 19.5 (7.0-83.2) cells/mm2 on awakening. Corresponding values for immature cells were 28.1 (5.8-112.5) cells/mm2, 22.3 (7.4-84.0) cells/mm2 and 18.0 (2.9-64.8) cells/mm2, and for mature cells, 3.1 (0.0-6.6) cells/mm2, 2.0 (0.8-16.8) cells/mm2, and 1.6 (0.2-8.2) cells/mm2. At the inferior whorl, total dendritic cell density was 38.5 (18.4-84.5) cells/mm2, 34.4 (9.4-82.3) cell/mm2, and 32.3 (15.2-96.1) cells/mm2. Immature cell density was 32.8 (18.4-80.9) cells/mm2, 34.4 (8.6-81.0) cells/mm2, and 32.3 (12.6-78.5) cells/mm2. Mature cell density was 1.6 (0.0-6.3) cells/mm2, 1.6 (0.0-3.1) cells/mm2, and 1.8 (0.0-6.3) cells/mm2. There was no significant difference between time points for total cell density (p > 0.05), but the percentage of mature cells upon awakening was significantly greater, compared to midday, at the central cornea (p = 0.02).Conclusion: In healthy individuals, overall corneal dendritic cell density is reasonably constant during the sleep/wake cycle, but the relative number of mature cells tends to increase overnight.

Corneal Nerve Parameter Reference Values for Chinese Adults Assessed by Corneal Confocal Microscopy.

Background: Confocal corneal microscopy is an excellent new noninvasive tool for assessing diabetic peripheral neuropathy. We aimed to investigate the clinical variables associated with corneal nerve parameters and establish reference values for clinical use in healthy Chinese adults. Methods: The study enlisted 257 healthy volunteers (137 females and 120 males) from two clinical academic centers in China. Two experts captured and selected images of the central corneal subbasal nerve plexus at each center using the same corneal confocal microscopy instrument according to a commonly adopted protocol. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were measured using fully automated software (ACCMetrics). The correlation between clinical indicators and confocal corneal microscopy measures was determined using partial correlation. Quantile regression was used to calculate reference values and estimate the effects of clinical factors on the normative values of confocal corneal microscopy measures. Results: Females had significantly higher CNFD, CNBD, and CNFL than males. There was no correlation between age, glycated hemoglobin (HbA1c), height, weight, body mass index (BMI), and any corneal nerve fiber parameter in both sexes. In either sex, age, weight, height, BMI, and HbA1c did not affect the 0.05th quantile values of any corneal nerve parameter. Conclusions: This study establishes sex-adjusted reference values for corneal confocal microscopy measures in Chinese adults and provides a reference for clinical practice and research with this technique.

Corneal Nerve Fiber and Sensitivity Loss After Repeated Intravitreal Anti-VEGF Injections: An In Vivo Confocal Microscopy Study.

PURPOSE: The purpose of this study was to investigate corneal sensation, subbasal nerve plexus (SBNP), and ocular surface symptoms in patients who underwent multiple intravitreal antivascular endothelial growth factor (anti-VEGF) injections for age-related macular degeneration (AMD) and diabetic macular edema (DME). METHODS: Forty patients with previous anti-VEGF intravitreal injections (20 AMD and 20 DME) and 30 healthy controls were included in this study. In vivo corneal confocal microscopy (IVCM) of the SBNP, corneal sensitivity measurement with a Cochet-Bonnet esthesiometer, noninvasive tear break-up times, and ocular surface disease score index (OSDI) calculation were performed for each participant. Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, corneal total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fiber fractal dimension parameters were obtained by automatic digital analysis. RESULTS: Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, and corneal nerve fiber fractal dimension in IVCM imaging and corneal sensitivity were significantly decreased in both AMD and DME groups compared with the control group. Corneal nerve fiber width and OSDI scores were significantly increased in AMD and DME groups compared with the control group. None of the IVCM parameters were significantly different between AMD and DME groups. Corneal sensitivity was decreased in patients with DME compared with patients with AMD. Tear break-up time was not different among the groups. CONCLUSIONS: Corneal SBNP parameters were affected, corneal sensitivity was decreased, and OSDI scores were increased in patients with multiple intravitreal anti-VEGF injections. IVCM parameters were not significantly different between AMD and DME groups.

Effect of herpes simplex keratitis scar location on bilateral corneal nerve alterations: an in vivo confocal microscopy study.

AIMS: To evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM). METHODS: Central and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 peripheral scars (PS)) using IVCM. Results were compared between patients and 24 age-matched controls. CSND was correlated to corneal sensation for all locations. RESULTS: Overall patients revealed significant decrease of CSND in the central and peripheral cornea (9.13±0.98 and 6.26±0.53 mm/mm2, p<0.001), compared with controls (22.60±0.77 and 9.88±0.49 mm/mm2). CS group showed a decrease in central (8.09±1.30 mm/mm2) and total peripheral nerves (5.15±0.62 mm/mm2) of the affected eyes, whereas PS group demonstrated a decrease in central (10.34±1.48 mm/mm2) and localised peripheral nerves only in the scar area (4.22±0.77 mm/mm2) (all p<0.001). In contralateral eyes, CSND decreased in the central cornea of the CS group (16.88±1.27, p=0.004), and in the peripheral area, mirroring the scar area in the affected eyes of the PS group (7.20±0.87, p=0.032). Corneal sensation significantly decreased in the whole cornea of the affected, but not in contralateral eyes (p<0.001). A positive correlation between CSND and corneal sensation was found in all locations (p<0.001). CONCLUSIONS: Patients with HSV scar demonstrate bilateral CSND decrease as shown by IVCM. CSND and corneal sensation decrease in both central and peripheral cornea in affected eyes, although only in the scar area in PS group. Interestingly, diminishment of CSND was found locally in the contralateral eyes, corresponding and mirroring the scar location in the affected eyes.

Corneal sub-basal nerve plexus microneuromas in individuals with and without dry eye.

BACKGROUND/AIM: An objective marker is needed to detect when corneal nerve abnormalities underlie neuropathic corneal pain (NCP), as symptoms often overlap with those of dry eye (DE). This study evaluated microneuroma (MN) frequency in various populations and investigated relationships between MN presence and DE clinical features in individuals with DE symptoms but without a history of refractive surgery, in order to eliminate refractive surgery as a potential confounder of nerve abnormalities. METHODS: This was a retrospective study that included individuals with and without DE symptoms who underwent a clinical evaluation for DE (symptom surveys and ocular surface evaluation) and in vivo confocal microscopy imaging. DE clinical features (including those suggestive of neuropathic pain) were compared based on MN presence using t-tests, χ2 analyses and Pearson's correlation coefficients with 0.05 alpha level. RESULTS: MN frequencies did not significantly differ between individuals with DE symptoms (Dry Eye Questionnaire 5 score ≥6) and a history of refractive surgery (n=1/16, 6%), individuals with DE symptoms without a history of refractive surgery (n=26/119, 22%) and individuals without DE symptoms (n=2/18, 11%, p=0.22). Among individuals with DE symptoms without a history of refractive surgery, DE clinical features, including those indicative of NCP (burning sensation and sensitivity to light, wind and extreme temperatures), did not significantly differ based on MN presence (p>0.05). CONCLUSION: MN frequencies did not significantly differ between individuals with and without DE symptoms. Their presence alone could not distinguish between DE subtypes, including features of NCP in our study population.

Corneal Sensation and Nerve Fiber Changes in Patients With Interstitial Cystitis.

PURPOSE: Central sensitization syndromes are associated with ocular surface discomfort and certain changes in corneal sensation. The aim of this study was to evaluate corneal changes in patients with interstitial cystitis (IC). METHODS: Thirty patients with IC and 32 healthy control subjects were included in this study. All patients had a detailed ophthalmological examination including measurement of corneal sensation with Cochet-Bonnet esthesiometer, tear breakup time, Schirmer I test, and Ocular Surface Disease Index questionnaire. After these examinations, corneal subbasal nerve plexus of the patients was evaluated with in vivo corneal confocal microscopy (IVCM) and the images were analyzed using fully automated software (ACC Metrics Corneal Nerve Fiber Analyzer V.2). RESULTS: There was no significant difference between the groups regarding age and gender distribution. Corneal sensation was significantly higher in patients with IC (P = 0.03), whereas tear breakup time, Schirmer I test, and Ocular Surface Disease Index scores were similar between the patients and controls. IVCM demonstrated nerve fiber loss in patients with IC. Corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length were significantly reduced in patients with IC compared with healthy controls (P < 0.001, P = 0.04, and P < 0.001, respectively). CONCLUSIONS: Patients with IC had increased corneal sensation and decreased nerve fiber density in IVCM analysis. Corneal nerve fiber loss might decrease the induction threshold of the remaining fibers to induce peripheral sensitization, which may also trigger central sensitization in long term.

Subbasal corneal nerve damage in patients with bacterial keratitis: in vivo confocal microscopy study.

PURPOSE: To examine subbasal corneal nerve changes in patients with bacterial infectious keratitis using in vivo confocal microscopy. METHODS: Thirteen patients (13 eyes) with unilateral bacterial keratitis and 12 healthy controls were prospectively enrolled in the study. In vivo confocal microscopy was performed in all the patients at 2 time points, in the acute phase of infectious keratitis and at 28 ± 0.6 months after resolution of the infection. RESULTS: The subbasal nerve length was 5.15 ± 1.03 mm/mm2 during the acute phase of bacterial keratitis (compared with that of the controls: 19.02 ± 1.78 mm/mm2, p<0.05). Despite the significant corneal nerve regeneration over the interval of 28 months after the resolution of the infection, the nerve density was still significantly reduced as compared with that of the controls (9.73 ± 0.93 mm/mm2, p<0.05). Moreover, in vivo confocal microscopy images showed diffuse high-reflecting areas referring to the scar tissue areas with thin and tortuous nerve branches regenerating toward these areas. CONCLUSIONS: A partial corneal nerve regeneration of subbasal nerve plexus during the first 28 months after the acute phase of infectious keratitis was observed. Moreover, the regenerated nerves of the patients remained morphologically altered as compared with those of the healthy controls. These results may be relevant to the clinical follow-up and surgical planning for these patients.

Orbital neuromuscular choristoma of the ophthalmic nerve.

INTRODUCTION: Neuromuscular choristoma (NC) is a rare tumor composed of striated muscle fibers admixed with nerve fibers that often affects large peripheral nerve trunks in children. To the best of our knowledge, this is the first reported case in the literature of a NC of the ophthalmic nerve in an adult. CASE DESCRIPTION: A 27-year-old woman presented with a 20-day history of left periorbital headache radiating to the frontotemporal region, with associated tearing, nausea, and vomiting. The examination was normal, except for hypoesthesia in the distribution of the first trigeminal nerve branch (V1). Cranial computerized tomography showed a lesion in the left orbit and cavernous sinus with widening of the superior orbital fissure. On magnetic resonance imaging, the lesion was well-defined with fusiform morphology and showed a central cystic component and peripheral enhancement. An extradural approach was performed with subtotal tumor resection. Biopsy showed proliferation of striated muscle cells admixed with nerve fascicles and Schwann cells. A pathological diagnosis of NC of V1 was determined. Six months after surgery, left hypotropia with limitation of supraduction was observed, as well as hypoesthesia and paralysis of the left forehead with ipsilateral eyebrow ptosis. The rest of the examination remained within normal limits. CONCLUSION: NC should be considered in the differential diagnosis of a young patient with periorbital headache and hypoesthesia in the V1 region.