Ocular Findings Associated with Hypoparathyroidism.

Purpose: To determine the corneal and retinal changes associated with serum calcium, phosphorus and parathyroid hormone (PTH) levels in patients with hypoparathyroidism.Methods: Patients who were under follow-up for hypoparathyroidism in the endocrinology department were included in the study. All participants underwent a complete ophthalmological examination. Moreover, central corneal thickness (CCT), anterior chamber depth (ACD), retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness were recorded. Serum biochemical parameters were recorded.Results: In a total of 75 patients (35 in the hypoparathyroidism group and 40 in the healthy control group) were included in this study. Central corneal thickness (519.95 ± 33.21 vs. 539.10 ± 32.96, p: 0.001) and RNFL (105.10 ± 11.89 vs. 113.56 ± 9.54, p: 0.005) were significantly thinner and ACD was significantly deeper in the hypoparathyroidism group.Conclusion: We determined thinner CCT and RNFL values in patients with hypoparathyroidism related to serum calcium levels together with a significant deepness in ACD.

Pregnancy-induced Changes in Corneal Biomechanics and Topography Are Thyroid Hormone Related.

PURPOSE: To identify biomechanical and topographic changes of the cornea during pregnancy and the postpartum period and its association to hormonal changes. DESIGN: Prospective single-center observational cohort study. METHODS: Participants were 24 pregnant women (48 eyes), monitored throughout pregnancy and after delivery. Biomechanical and topographic corneal properties were measured using the Ocular Response Analyzer (ORA) and a Scheimpflug imaging system (Pentacam HR) each trimester and 1 month after delivery. At the same consultations blood plasma levels of estradiol (E2) and thyroid hormones (TSH, T3t, T4t) were also determined. A factorial MANCOVA was used to detect interactions between hormonal plasma levels and ocular parameters. RESULTS: Significant differences in corneal biomechanical and topographic parameters were found during pregnancy in relation to T3t (p = .01), T4t (p < .001), T3t/T4t (P = .001), and TSH (p = .001) plasma levels. E2 plasma levels (p = .092) and time period of measurement (p = .975) did not significantly affect corneal parameters. TSH levels significantly affected the maximal keratometry reading (p = .036), the vertical keratometry reading (p = .04), and the index of height asymmetry (p = .014). Those results persist after excluding hypothyroidism patients from the statistical analysis. CONCLUSIONS: Hormonal changes affecting corneal biomechanics and topography during pregnancy could be thyroid related. Dysthyroidism may directly influence corneal biomechanics and represents a clinically relevant factor that needs further investigation.

Validity of Postmortem Glycated Hemoglobin to Determine Status of Diabetes Mellitus in Corneal Donors.

PURPOSE: To examine the stability of postmortem glycated hemoglobin (HbA1c) measurement and its relationship to premortem glycemia. METHODS: Postmortem blood samples were obtained from 32 donors (8 known diabetic) and shipped on ice to a central laboratory to examine the stability of HbA1c measurements during the first 9 postmortem days. Thirty-nine other suspected diabetic donors underwent comparison of premortem and postmortem HbA1c measurements. RESULTS: Postmortem HbA1c measurements remained stable after 9 postmortem days (all measurements within ±0.2% from baseline with a mean difference of 0.02% ± 0.10%). Of the premortem measurements obtained within 90 days before death, 79% were within ±1.0% of the postmortem measurements compared with 40% for measurements more than 90 days apart. Three of the postmortem HbA1c measurements exceeded 6.5% (considered a threshold for diabetes diagnosis), although the medical histories did not indicate any previous diabetes diagnosis. CONCLUSIONS: Postmortem HbA1c testing is feasible with current eye bank procedures and is reflective of glycemic control of donors during 90 days before death. HbA1c testing could potentially be a useful adjunct to review of the medical history and records for donor assessment for endothelial keratoplasty suitability and long-term graft success.

Undiluted Serum Eye Drops for the Treatment of Persistent Corneal Epitheilal Defects.

Several studies found that 50-100% serum eye drops provided greater benefits without inducing detrimental effects on the corneal epithelial healing. This study assessed the efficacy of undiluted serum eye drops for the treatment of persistent corneal epithelial defects (PED). A total of 109 eyes received 100% serum eye drops for PED were recruited into this study. The data were compared with an historical control group of 79 eyes with PED who received conventional treatments from 2006-2011 at the same institution. Main outcome measures were complete healing of PED and incidence of adverse events. No significant difference in demographics between the 2 groups was noted. The success rate of the treatment and control groups were 87.16% (95% CI 0.79-0.93) and 69.62% (95% CI 0.59-0.80) (P = 0.001), respectively. The median time to complete epithelialization was 14 days (95% CI 12-21) in the treatment group and 28 days (95% CI 21-59) in the control group (P = 0.001). Serum treatment, primary diagnosis of non-limbal stem cell deficiency etiology, and prior contact lens wear significantly correlated with the corneal re-epithelialization. There were no serious side effects encountered during the study period. In conclusion, undiluted serum therapy is effective and safe for treating PED.

Corneal Endothelial Alterations in Chronic Renal Failure.

PURPOSE: To evaluate the corneal endothelial changes in patients with chronic renal failure. METHODS: A total of 128 corneas of 128 subjects were studied, and 3 groups were formed. The first, the dialyzed group, composed of 32 corneas of 32 patients; the second, the nondialyzed group, composed of 34 corneas of 34 patients; and the third, the age-matched control group, composed of 64 corneas of 64 healthy subjects were examined by a specular microscope and the endothelial parameters were compared. The dialyzed group (enhanced level of toxins in the blood) was further analyzed to assess the influence of blood urea, serum creatinine, serum calcium, and serum phosphorus including the duration of dialysis on corneal endothelium. RESULTS: On comparing the 3 groups using analysis of variance and posthoc tests, a significant difference was found in the central corneal thickness (CCT) and endothelial cell density (CD) between the control (CCT: 506 ± 29 µm, CD: 2760 ± 304 cells/mm) and dialyzed groups (CCT: 549 ± 30 µm, CD: 2337 ± 324 cells/mm) [P < 0.001 (CCT); P < 0.001 (CD)]; control and nondialyzed groups (CCT: 524 ± 27 µm, CD: 2574 ± 260 cells/mm) [P = 0.023 (CCT); P = 0.016 (CD)]; and dialyzed and nondialyzed groups [P = 0.002 (CCT); P = 0.007 (CD)]. Using the linear generalized model, a significant correlation was found between the endothelial parameters and blood urea only [P = 0.006 (CCT), 0.002 (coefficient of variation), 0.022 (CD), and 0.026 (percentage of hexagonality)], although the correlation was poorly positive for CCT but poorly negative for the remaining endothelial parameters. CONCLUSIONS: Corneal endothelial alteration is present in patients with chronic renal failure, more marked in patients undergoing hemodialysis and with raised blood urea level.

The Hematologic Definition of Monoclonal Gammopathy of Undetermined Significance in Relation to Paraproteinemic Keratopathy (An American Ophthalmological Society Thesis).

PURPOSE: To determine if paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of undetermined significance (MGUS) causes distinct patterns of corneal opacification that can be distinguished from hereditary, immunologic, or inflammatory causes. METHODS: A retrospective, interventional study of patients showed distinct bilateral opacity patterns of the cornea at the eye clinics of Hanau, Mainz, Helsinki, Marburg, and Berlin between 1993 and 2015. Data on patient characteristics and clinical features on ophthalmic examination were collected, and serum protein profiles were evaluated. A literature review and analysis of all published studies of MGUS with PPK is also presented. RESULTS: The largest group of patients diagnosed with MGUS-induced PPK is analyzed in this study. We studied 22 eyes of 11 patients (6 male, aged 43 to 65, mean age 54; 5 female, aged 49 to 76, mean age 61) with distinct corneal opacities and visual impairment who were first suspected of having hereditary, inflammatory, or immunologic corneal entities. Subsequently, serum protein electrophoresis revealed MGUS to be the cause of the PPK. Literature review revealed 72 patients with bilateral PPK (34 male, mean age 57; 38 female, mean age 58) in 51 studies of MGUS published from 1934 to 2015 and disclosed six additional corneal opacity patterns. CONCLUSIONS: This thesis shows that MGUS is not always an asymptomatic disorder, in contrast to the hematologic definition, which has no hint of PPK. The MGUS-induced PPK can mimic many other diseases of the anterior layer of the eye. A new clinical classification for PPK in MGUS is proposed.

Hypercholesterolemia-induced ocular disorder: Ameliorating role of phytotherapy.

The ocular region is a complex structure that allows conscious light perception and vision. It is of ecto-mesodermal origin. Cholesterol and polyunsaturated fatty acids are involved in retinal cell function; however, hypercholesterolemia and diabetes impair its function. Retinal damage, neovascularization, and cataracts are the main complications of cholesterol overload. Dietary supplementation of selected plant products can lead to the scavenging of free reactive oxygen species, thereby protecting the ocular regions from the damage of hypercholesterolemia. This review illustrates the dramatic effects of increased cholesterol levels on the ocular regions. The effect of phytotherapy is discussed in relation to the different regions of the eye, including the retina, cornea, and lens.

Correlation between conjunctival and corneal calcification and cardiovascular calcification in patients undergoing maintenance hemodialysis.

The purpose of this study was to investigate the correlation of conjunctival and corneal calcification (CCC) with cardiovascular calcification in patients undergoing maintenance hemodialysis (MHD). A total of 122 patients undergoing MHD in our hospital were included in this study. Conjunctival and corneal calcification was examined by slit lamp and graded. Abdominal aortic calcification (AAC), aortic valve calcification (AVC), and mitral valve calcification (MVC) were determined by X-ray or ultrasound. The correlation of CCC with AAC, AVC, and MVC was analyzed. Biochemical, hematological, and cardiovascular data were compared between patients with different severity of CCC or AAC. Mitral valve calcification was significantly associated with AAC in our patients. Conjunctival and corneal calcification positively correlated with AAC. We also found that patients with severe CCC exhibited significantly higher levels of serum calcium, phosphate, product of calcium and phosphate, serum copper, cystatin, intact parathyroid hormone, and vitamin D than patients with mild CCC. In addition to significantly increased levels of serum calcium, product of calcium and phosphate, serum copper, and cystatin, patients with severe AAC also had higher high-sensitivity C-reactive protein level and greater left ventricular posterior wall thickness and left ventricular end-diastolic interventricular septum thickness than patients with mild AAC. Our results suggest that patients undergoing MHD with severe CCC or AAC have high degree of mineral metabolism disorder, inflammation, and cardiovascular function disorder. The strong correlation between CCC and AAC indicates that CCC score might be used as an indirect indicator to predict cardiovascular risks in patients undergoing MHD.

Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis.

PURPOSE: Platelet-rich plasma (PRP) harbors high concentrations of growth factors related to the promotion of wound healing. We evaluated the efficacy of PRP eyedrops in the treatment of persistent epithelial defects (PEDs). METHODS: Autologous PRP and autologous serum (AS) were prepared from whole blood. The concentrations of transforming growth factor (TGF)-ß1, TGF-ß2, epidermal growth factor (EGF), vitamin A and fibronectin in the PRP and AS were analyzed and compared. The corneal epithelial healing efficacy of PRP was compared with that of AS in patients with PED induced by post-infectious inflammation. RESULTS: The concentrations of TGF-ß1, TGF-ß2, EGF, vitamin A and fibronectin in the PRP and AS were not statistically different. However, the concentrations of EGF in the PRP were significantly greater than in the AS. AS was used in 17 and PRP in 11 eyes of 28 patients. The healing rates of the corneal epithelia of the PRP-treated eyes were significantly higher than those treated with AS. CONCLUSIONS: The PRP was effective in the treatment of PEDs. This may be attributable to its high concentration of platelet-contained growth factors, most notably EGF. PRP could be an effective, novel treatment option for chronic ocular surface disease.

Oral alcohol administration disturbs tear film and ocular surface.

PURPOSE: To investigate whether ethanol administration disturbs the tear film and ocular surface. DESIGN: Case-control study. PARTICIPANTS: Twenty healthy male subjects were recruited. Ethanol was administered to 10 subjects and another 10 subjects served as controls. METHODS: Twenty healthy male subjects with no ocular disease were recruited. Ethanol (0.75 g/kg) was administered orally at 8 pm for 2 hours to 10 subjects. MAIN OUTCOME MEASURES: The tear film and ocular surface were evaluated at 6 pm before drinking, at midnight, and immediately (6 am) and 2 hours (8 am) after waking the next morning. Tear osmolarity, ethanol concentration in tears and serum, Schirmer's test results, tear film break-up time (TBUT), corneal punctuate erosion, and corneal sensitivity were measured. RESULTS: Ethanol was detected in tears and serum at midnight, but it was not detected the next morning. The mean tear osmolarity level increased in the alcohol group at midnight compared with that in the control group (P<0.001). The alcohol group showed a significantly shorter TBUT compared with the control group after drinking alcohol (P<0.001 at 12 am, P<0.001 at 6 am, and P = 0.002 at 8 am). There were significantly higher fluorescein staining scores in the alcohol group compared with those in the control group at 6 am and 8 am (P = 0.001 and P<0.001, respectively). No significant change was shown in corneal sensitivity or Schirmer's test results in either group. CONCLUSIONS: Orally administered ethanol was secreted into the tears. Ethanol in tears induced tear hyperosmolarity and shortened TBUT and triggered the development of ocular surface diseases. Similar changes could exacerbate signs and symptoms in patients with ocular surface disease.

Richner-Hanhart syndrome (tyrosinemia type II): a case report of delayed diagnosis with pseudodendritic corneal lesion.

Richner-Hanhart syndrome (tyrosinemia type II) is a rare autosomal recessive disease associated with high serum tyrosine levels caused by the deficiency of tyrosine aminotransferase enzyme. We report a 15-year-old female patient with complaints of bilateral photophobia and tearing, which started during the infancy period. Biomicroscopic examination revealed bilateral circular corneal opacities on the inferior quadrant and small dendritic lesions at the center of the circular opacities. Blood tests showed a tyrosine level of 508 micromol/L (normal range: 30-150). On her dermatologic examination, plantar hyperkeratosis and seborrheic dermatitis were noted, and mild mental retardation was detected. One and a half months after the tyrosine- and phenylalanine-restricted diet, her tyrosine level dropped to 395 micromol/L level, her corneal lesions subsided, and a symptomatic relief was achieved. Tyrosinemia type II should be suspected in patients demonstrating dermatologic signs, especially palmoplantar keratosis, associated with bilateral pseudodendritic corneal lesions unresponsive to antiviral therapy.

Long-term follow up of autologous serum treatment for recurrent corneal erosions.

PURPOSE: The aim of the study was to evaluate long-term results of autologous serum treatment for recurrent corneal erosions. METHODS: In this prospective single-centre study, 33 eyes of 33 patients (21 male and 12 female) were treated with autologous serum eye drops for recurrent corneal erosions. Mean age of the patients was 49.3 ± 9.8 standard deviation (range 24-73) years. All subjects had failed to respond to other treatments. Autologous serum drops were administered for a 6-month period: six times daily for the first 3 months and four times daily for the remaining 3 months. Detailed informed consent was obtained from the entire patient group before the study. RESULTS: The mean follow-up period was 30 ± 6.3 standard deviation (range 12-48) months. None of the patients experienced a recurrence while under treatment. Twenty-eight patients (85%) had complete healing of erosions with no relapses of the disease over the whole follow-up period. Five patients (15%) presented a single recurrence 3-12 months after the end of the treatment. No sight-threatening complications were reported over the follow up. There was no statistically significant difference in the best spectacle-corrected visual acuity values (t(stat) = 2.1, F = 0.096, degree of freedom = 40,166, P < 0.41) or in the intraocular pressure measurements (P < 0.38) between the pre- and post-treatment patient groups. CONCLUSIONS: Autologous serum drops proved to be a safe and efficient treatment modality for patients with recurrent corneal erosion syndrome as observed through a long-term follow up.

Autologous serum eyedrops in the treatment of aniridic keratopathy.

OBJECTIVE: To study the effect of autologous serum eyedrop application in aniridic keratopathy. DESIGN: Prospective, consecutive, comparative, interventional case series. PARTICIPANTS: Twenty-six eyes from 13 patients (7 males and 6 females) with aniridic keratopathy treated with autologous serum eyedrops. METHODS: All patients underwent a complete ophthalmic examination. The ocular surface examinations included corneal impression cytologic analysis and tear film evaluation. The eyes were divided into 4 groups according to the Mackman classification. Ocular surface photography was used to evaluate the corneal surface and tear film before treatment and every 2 or 3 days until serum drops were stopped. Tear films were evaluated by tear film break-up time (BUT) (normal, 10 seconds or more), Schirmer's test with anesthesia (normal, 10 mm/5 minutes or more), tear meniscus level (normal, 0.5 mm or more), and rose bengal and fluorescein staining pattern of the cornea. Impression cytologic analysis was carried out both before starting the serum eyedrops treatment and a few days after its finalization. MAIN OUTCOMES MEASURES: Tear film production and stability, corneal epithelialization, and corneal epithelium squamous metaplasia. RESULTS: There were no local side effects from autologous serum treatment. Clinical manifestations and slit-lamp findings were in relation to the severity of keratopathy. All patients showed a subjective improvement of keratopathy symptoms after the autologous serum applications. The corneal epithelialization, corneal epithelial cell squamous metaplasia, and tear stability improved significantly with the treatment, but visual acuity, regression of vascular pannus, and subepithelial scarring showed only slight improvement with treatment. CONCLUSIONS: Autologous serum eyedrops improved the aniridic keratopathy in all patients, particularly in patients with light or moderate severity. In these patients, use of autologous serum eyedrops was superior to conventional therapy with substitute tears for improving the ocular surface and subjective comfort.

Evidence against a blood derived origin for transforming growth factor beta induced protein in corneal disorders caused by mutations in the TGFBI gene.

PURPOSE: Several inherited corneal disorders in humans result from mutations in the transforming growth factor beta induced gene (TGFBI), which encodes for the extracellular transforming growth factor beta induced protein (TGFBIp) that is one of the most abundant proteins in the cornea. We previously reported a significant amount of TGFBIp in plasma by immunoblotting using the only TGFBIp antiserum (anti-p68(beta ig-h3)) available at that time (anti-p68(beta ig-h3) was generated against residues Val210-His683 of TGFBIp). This observation raised the possibility that a fraction of corneal TGFBIp may originate from the plasma. However, recent experiments in our laboratory indicated that the anti-p68(beta ig-h3) antiserum cross-reacts with an environmental protein contaminant. Therefore, we investigated the specificity of the originally utilized anti-p68(beta ig-h3) antiserum and re-evaluated the amount of TGFBIp in human plasma by immunoblotting using a new specific antiserum. METHODS: The observed cross-reactivity of the previously utilized anti-p68(beta ig-h3) antiserum was tested by immunoblotting and the antigen identity was determined by mass spectrometry. A part of human TGFBI encoding an NH2-terminal 11.4 kDa fragment of TGFBIp (residues Gly134-Ile236) was amplified by polymerase chain reaction (PCR) and cloned in E. coli. The TGFBIp fragment was expressed in E. coli, purified by Ni2+-affinity chromatography, and used to immunize rabbits to produce a specific antiserum (anti-TGFBIp(134-236)). To enhance the detection of possible TGFBIp in plasma by allowing a higher sample load, albumin and immunoglobulin G (IgG) were specifically depleted from normal human plasma by affinity chromatography. The presence of TGFBIp in plasma was investigated by immunoblotting using the anti-TGFBIp(134-236) antiserum. Purified TGFBIp from porcine corneas was used for estimation of the TGFBIp detection limit. RESULTS: The previously utilized TGFBIp antiserum, anti-p68(beta ig-h3), cross-reacted with human keratin-1, a common environmental protein contaminant. Thus, the anti-p68(beta ig-h3) antiserum recognizes both TGFBIp and keratin-1. In contrast, the anti-TGFBIp(134-236) antiserum reacted with TGFBIp but showed no indication of reactivity with other proteins in plasma. Using this antiserum, TGFBIp was not detected in crude or albumin/IgG-depleted human plasma and the detection limit of TGFBIp using immunoblotting was estimated to be 10 ng. CONCLUSIONS: Our failure to detect TGFBIp in human plasma using a highly specific antiserum suggests that TGFBIp is not present in a physiologically relevant concentration in human plasma. The previous impression that normal human plasma contains a significant amount of TGFBIp by immunoblotting was due to the utilization of a less specific antiserum that recognizes both TGFBIp and human keratin-1. Together with other results, our observation makes it unlikely that TGFBIp is imported into the cornea from the circulation as reported for other abundant extracellular corneal proteins and suggests corneal origin of TGFBIp deposits in individuals with inherited corneal diseases caused by mutations in the TGFBI gene.

Autologous serum-derived cultivated oral epithelial transplants for severe ocular surface disease.

OBJECTIVE: To evaluate the use of autologous serum (AS)-derived cultivated oral epithelial transplants for the treatment of severe ocular surface disease. METHODS: We used AS from 10 patients with severe ocular surface disease and total limbal stem cell deficiency to develop autologous cultivated oral epithelial equivalents. These were compared with epithelial equivalents derived from conventional fetal bovine serum-supplemented medium. Surgery involved removal of the corneal pannus and surrounding diseased tissue and transplantation of the AS-derived epithelial equivalents. The oral equivalents were analyzed by review of histologic and immunohistochemical findings. RESULTS: Oral epithelial sheets cultivated in AS- and fetal bovine serum-supplemented media were similar in morphology, and both formed basement membrane assembly proteins important for maintaining graft integrity. Complete corneal epithelialization was achieved within 2 to 5 days postoperatively. The ocular surface remained stable without major complications in all eyes during a mean +/- SD follow-up of 12.6 +/- 3.9 months. The visual acuity improved by more than 2 lines in 9 of 10 eyes, with transplanted oral epithelium surviving up to 19 months. CONCLUSION: The successful use of an AS-derived oral epithelial equivalent to treat severe ocular surface disease represents an important advance in the pursuit of completely autologous xenobiotic-free bioengineered ocular equivalents for clinical transplantation.

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of coronary heart disease among US women.

OBJECTIVE: Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5), and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). METHOD AND RESULTS: We examined seven common variants in the CCR2 and CCR5 loci and risk of CHD among women in the Nurses' Health Study. During 8 years of follow-up, we documented 248 incident cases of nonfatal myocardial infarction and fatal CHD, and matched controls 2:1 based on age and smoking. The distribution of alleles was similar between cases and controls. The haplotype-specific odds ratios (ORs) were not statistically significant nor was the globally-adjusted p-value (p=0.61). However, there was a statistically significant association for CCR5-Delta32 and A58755G (rs2856758) between cases and controls comparing age of onset <55 and >or=55 years. For Delta32, the OR for having the variant was 0.12 (0.02-0.76) for age <55, and 1.14 (0.69-1.88) for age >or=55 years (p, interaction=0.04). The CCR5-Delta32 was in linkage disequilibrium with 58755G, and a similar association was observed for having the 58755G. CONCLUSIONS: In this population, CCR2-CCR5 haplotypes were not associated with risk of CHD. However, our data suggest a strong inverse association for certain CCR5 variants and early age of CHD onset.

[Effect of lamellar keratoplasty time on the production of serum specific antibody in corneal alkali burns].

OBJECTIVE: To observe the production of serum specific anti-denatured corneal antibody and the effects of lamellar keratoplasty on changes of corneal histopathology in different stages after alkali burns. METHODS: 20 male New Zealand rabbits, with alkali burns in right eye were randomly divided into 5 groups including: burned group; 2 early lamellar keratoplasty group (operation at 3 or 7 days post alkali burns respectively); 2 middle and later lamellar keratoplasty groups (operation at 2 or 5 weeks after alkali burns respectively). The level of serum specific antibody in each group was detected by ELISA and the corneal structure was evaluated by light and electron microscopy in different stages after alkali burns. RESULTS: The anti-denatured corneal antibody was induced after corneal alkali burns. The level of antibody significantly increased at 2th week post, peaking burn at 5 or 6th week, then decreasing. More antibodies were detected when contralateral eye was burn at 8 week post first burn. However, only slight increasing antibody was detected in early lamellar keratoplasty group. Furthermore, no significant changes of antibody production were observed in middle and later lamellar keratoplasty group. The light and electron microscopic analysis showed that, the corneal epithelium recovered better, the fibre of corneal stroma arranged better, inflammatory cells infiltrated less and neovascularization formed less in lamellar keratoplasty groups comparing to the burned group. The early lamellar keratoplasty groups recovered better than in middle and later lamellar keratoplasty groups. CONCLUSION: Early lamellar keratoplasty after corneal alkali burns can significantly decrease the immune response. Histopathological data also indicate that early lamellar keratoplasty can improve the tissue regeneration and recovery, prevent topical inflammatory reaction, and abate corneal neovascularization. This study suggests that early lamellar keratoplasty is more effective than the conservative treatment.

Autologous serum application in the treatment of neurotrophic keratopathy.

OBJECTIVE: To evaluate the effect of autologous serum application for epithelial disorders in neurotrophic keratopathy (NK). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Fourteen eyes of 11 patients with NK seen at Tokyo Dental College, Ichikawa General Hospital, Department of Ophthalmology, were studied. INTERVENTION: Twenty percent topical autologous serum eye drops were applied 5 to 10 times daily until resolution of the NK. Patients underwent routine ophthalmic examinations, including slit-lamp examination, corneal fluorescein dye testing, Cochet-Bonnet corneal sensitivity (Luneau, France), and best-corrected visual acuity (BCVA) measurements before and at the end of the treatment. Moreover, serum samples from 10 healthy volunteers were studied for the levels of substance P (SP), insulinlike growth factor (IGF-1), and nerve growth factor (NGF) by using radioimmunoassay and enzyme-linked immunosorbent assay techniques. Tear samples from 3 healthy subjects also were analyzed for NGF and IGF-1 levels by the same techniques. MAIN OUTCOME MEASURES: The changes in corneal disease state, corneal sensitivity, and BCVA with treatment were evaluated. The levels of neural healing factors like SP, IGF-1, and NGF in serum as well as NGF and IGF-1 in tears of healthy subjects also were examined. RESULTS: The epithelial disorders healed completely in all eyes within 6 to 32 days (mean, 17.1+/-8.0 days), with a decrease in corneal scarring. The mean pretreatment corneal sensitivity was 11.8+/-11.6 mm, which increased to 30.0+/-22.9 mm after treatment at the last follow-up. Five eyes attained normal corneal sensitivity with treatment. The BCVA improved by >2 Landolt lines in 78.6% of the eyes. The mean concentrations of SP in diluted and undiluted serum were 31.4+/-8.4 pg/ml and 157.0+/-42.1 pg/ml, respectively. The mean respective concentrations of IGF-1 in diluted and undiluted serum were 31.4+/-14.8 ng/ml and 157.0+/-73.9 ng/ml. The mean concentrations for NGF were 93.6+/-63.5 pg/ml and 468.3+/-317.4 pg/ml in serum samples with and without dilution, respectively. The mean concentration of NGF in tears was found to be 54 pg/ml. Insulinlike growth factor 1 was not detected in tears in this study. CONCLUSIONS: Autologous serum harbors neurotrophic factors. Autologous serum treatment may provide neural healers to the compromised ocular surface and seems promising for the restoration of the ocular surface epithelial integrity in patients with NK.