Potential role of tumor-infiltrating T-, B-lymphocytes, tumor-associated macrophages and IgA-secreting plasma cells in long-term survival in the rectal adenocarcinoma patients.

AIMS: Many studies investigated the associations between the role of immune cells of rectal cancer microenvironment and survival during the first 5 years post-surgery. This is problematic as this disease has the potential to progress even after 5 years after relapse and infiltrating immune cells could play key roles. Therefore, this retrospective study investigates expression and roles of tumor-infiltrating T-lymphocytes (TIL-T), tumor-infiltrating B-lymphocytes (TILB), IgA+ plasma cells (IgA+ PC) and tumor-associated macrophages (TAM) in patients with or without progression over 5 years survival with rectal adenocarcinoma. MAIN METHODS: Here we used immunohistochemical staining of CD3, CD20, IgA, CD68 positive cells and its detection in rectal cancer stroma. Data was analyzed using Mann Whitney U test, ROC, survival and Cox's regression analysis. KEY FINDINGS: The number of TIL-T (p = 0.0276), TIL-B (p < 0.0001) and IgA+ PC (p = 0.015) immune cells was significantly higher in rectal cancer stroma of patients with favorable outcome. Univariate Cox's regression analysis revealed a predictive role of TIL-T (HR = 0.482; 95% CI, 0.303 to 0.704; p < 0.0001), TIL-B (HR = 0.301; 95% CI, 0.198 to 0.481; p < 0.0001) and IgA+-PC (HR = 0.488; 95% CI, 0.322 to 0.741; p < 0.0001). Multivariate Cox's regression analysis showed prognostic role of TIL-B (HR = 0.940; 95% CI, 0.914 to 0.968; p < 0.0001) and IgA+-PC (HR = 0.985; 95% CI, 0.975 to 0.996; p = 0.006) play role in long time survival. SIGNIFICANCE: CD20+ TIL-B and IgA+ cells have significant associations with long -term survival of patients with rectal cancer, with potential therapeutic intervention in cancer immunotherapy.

Treatment results in aphakic patients with glaucoma following congenital cataract surgery.

PURPOSE: To evaluate the clinical findings and possible risk factors of patients with aphakic glaucoma following congenital cataract surgery and identify the factors affecting response to glaucoma treatment. METHODS: A retrospective chart review of 173 patients was performed who underwent congenital cataract surgery before the age of 12 months and 40 eyes of 25 patients with aphakic glaucoma were enrolled. Age of the patients at the time of the cataract surgery, postoperative complications, additional ocular pathologies and the type of glaucoma treatment needed were investigated. RESULTS: Mean age of 25 patients at the time of cataract surgery was 3.31 ± 2.28 (range 1-11) months with a mean follow-up period of 79 ± 30.5 (32-176) months. Out of 40 eyes, medical therapy was effective in 20 (50%) eyes, whereas 20 (50%) eyes needed surgery for glaucoma. In these 20 eyes, 6 (30%) eyes underwent only 1, 4 (20%) eyes underwent 2 and 10 (50%) eyes underwent 3 or more procedures. Age at the time of cataract surgery, pupillary membrane formation and additional ocular pathologies were not significantly associated both with the need for glaucoma surgery or the number of operations (p ≥ 0.05). CONCLUSION: Aphakic glaucoma following congenital cataract surgery is a serious complication which requires surgery in half (50%) of the patients. Usually, more than one surgical procedure (70%) is needed. It can be detected even years after cataract surgery (range 0.3-94 months), so long-term careful follow-up is necessary.

Long-term Results in Pediatric Developmental Cataract Surgery with Primary Intraocular Lens Implantation.

OBJECTIVES: The aim of this study was to evaluate the outcomes of pediatric developmental cataract surgery with primary intraocular lens (IOL) implantation. MATERIALS AND METHODS: Patients between 2 and 16 years old who underwent cataract surgery with primary IOL implantation were retrospectively evaluated. Age at time of surgery, pre- and postoperative best corrected visual acuities, postoperative ocular complications, and any accompanying ocular pathologies were obtained from the patients' charts. Mean refractive changes and degree of myopic shift were analyzed according to the age groups. Operated eyes were also compared with the fellow eyes in unilateral cases. RESULTS: A total of 101 eyes of 65 patients were included. The average age at time of surgery was 76±40 months and the average follow-up period was 44±30 months. Among the 78 eyes that could be assessed for visual acuity improvement, 66 (84.6%) of them showed ≥2 lines of improvement. The difference in the mean refractive change between the 2-5 years old and 8-16 years old age groups was found to be statistically significant. However, the mean refractive change per year was not found to be significant between the same age groups. In unilateral cases, the operated eyes showed a greater myopic change than the fellow eyes, with no statistically significant difference. The most common postoperative complication was visual axis opacity. CONCLUSION: Good visual outcomes can be achieved following pediatric cataract surgery with primary IOL implantation. Optic axis opacities were the most common postoperative complications. Overall, refractive changes following surgery are inevitable, and more prominent in younger age groups.

Factors Affecting Contrast Sensitivity in Healthy Individuals: A Pilot Study.

OBJECTIVES: To determine the demographic and ocular features affecting contrast sensitivity levels in healthy individuals. MATERIALS AND METHODS: Seventy-four eyes of 37 subjects (7-65 years old) with refractive errors less than 1.0 diopter, no history of ocular surgery, and 20/20 visual acuity were included in the study. The participants were divided by age into three groups: group 1, 7-19 years, n=11; group 2, 20-49 years, n=15; and group 3, 50-65 years, n=11. All subjects underwent anterior and posterior segment evaluation, intraocular pressure measurements, refraction measurements, and clinical evaluation for strabismus. Contrast static test was performed using Metrovision MonPack 3 vision monitor system after measuring pupil diameter. Photopic and mesopic measurements were taken sequentially from right eyes, left eyes, and both eyes together. RESULTS: Contrast sensitivity at intermediate and high spatial frequencies was lower with increasing age. Binocular measurements were better than monocular, and mesopic measurements were better than photopic measurements at all spatial frequencies. Contrast sensitivity at higher spatial frequency was lower with hyperopic refraction values. CONCLUSION: Increasing age, small pupil diameter, hyperopia, and photopic conditions were associated with lower contrast sensitivity in healthy individuals. Binocular contrast sensitivity measurements were better than monocular contrast sensitivity measurements in all conditions and spatial frequencies.

Strabismus in infants following congenital cataract surgery.

PURPOSE: This study aimed to determine the incidence and characteristics of strabismus following congenital cataract surgery in infants. MATERIALS AND METHODS: Patients aged <12 months who underwent surgery for congenital cataract and were followed-up for ≥1 years were included. Patients that had strabismus prior to surgery were excluded. Data regarding gender, cataract laterality, morphology, and density, age at the time of cataract surgery, ocular motility post surgery, and the presence of nystagmus were retrospectively obtained from the patients' records. RESULTS: The study included 79 patients (48 male and 31 female). Unilateral surgery was performed in 14 of the patients, versus bilateral surgery in 65. Strabismus did not occur post surgery in 32 (40.5 %) of the patients (group 1), whereas 47 (59.5 %) (group 2) developed strabismus following surgery. The patients in group 1 were followed-up for a mean 50.7 ± 38.5 months, versus 50.3 ± 39 months in group 2. Mean age at the time of cataract surgery in groups 1 and 2 was 3.6 ± 1.9 years and 4.6 ± 3.2 months respectively. Mean duration of time between cataract surgery and the development of strabismus was 13.3 ± 13 months (range: 1-60 months). Unilateral cases were more prone to develop strabismus, which was statistically significant (p = 0.028). Age at the time of cataract surgery, gender, cataract density, the occurrence of aphakic glaucoma, the presence of nystagmus, and additional ocular surgery were not significantly associated with the development of strabismus. CONCLUSION: Strabismus develops more frequently in children undergoing cataract surgery. In the present study strabismus occurred in more of the patients that underwent unilateral surgery. Based on the present findings, we think that long-term careful follow-up to monitor the development of strabismus is required in all infants undergoing cataract surgery, especially unilateral cases.

The impact of prism adaptation test on surgical outcomes in patients with primary exotropia.

BACKGROUND: We aimed to determine the impact of the preoperative prism adaptation test (PAT) on surgical outcomes in patients with primary exotropia. METHODS: Thirty-eight consecutive patients with primary exotropia were enrolled. Pre-operative PAT was performed in 18 randomly selected patients (Group 1). Surgery was based on the angle of deviation at distance measured after PAT. The remaining 20 patients in whom PAT was not performed comprised Group 2. Surgery was based on the angle of deviation at distance in these patients. Surgical success was defined as ocular alignment within eight prism dioptres (PD) of orthophoria. RESULTS: Satisfactory motor alignment (± 8 PD) was achieved in 16 Group 1 patients (88.9 per cent) and 16 Group 2 patients (80 per cent) one year after surgery (p = 0.6; chi-square test). There were no statistically significant differences in demographic parameters, pre-operative and post-operative angle of deviation between the two groups (p > 0.05; Mann-Whitney U and chi-square tests). Nine patients in Group 1 (50 per cent) and two patients in Group 2 (10 per cent) had increased binocular vision one year post-operatively. A statistically significant difference was determined in terms of change in binocular single vision between the two groups (p = 0.01; chi-square test). CONCLUSION: Although the prism adaptation test did not lead to a significant increment in motor success, it may be helpful in achieving a more favourable functional surgical outcome in patients with primary exotropia.

Influences of cyclopentolate hydrochloride on anterior segment parameters with Pentacam in children.

PURPOSE: To investigate the effects of cyclopentolate hydrochloride 1% on the main numerical parameters of anterior segment with Pentacam rotating Scheimpflug camera in children. SETTING: Ege University Faculty of Medicine, Department of Ophthalmology. METHODS: Pentacam measurements of 50 (23 boys and 27 girls) children before and after 45 min of cyclopentolate hydrochloride 1% instillation were performed and compared with 31 (17 boys and 14 girls) no medication instilled control group. Measurements of the control group (cycloplegia-free) were taken at two separate sessions with 45-min intervals. For comparison of the test parameters, paired t-test in the groups and unpaired t-test in between the groups were used. RESULTS: Mean ages in the study and control groups were 10.06 ± 2.87 (range 6 and 16 years) and 9.87 ± 2.72 (range 6 and 16 years), respectively, and the difference was statistically insignificant (p > 0.05). In the study group, measurements between two sessions were significantly different for the parameters of anterior chamber depth (ACD), anterior chamber volume (ACV) and central corneal thickness (CCT) (p < 0.05), whereas none of the parameters was different between two sessions for control group. CONCLUSIONS: Cyclopentolate hydrochloride 1% instillation leads to significant decrement in CCT. ACD and ACV are the other important refractive parameters that increase significantly after cycloplegia. Effects of cycloplegia on these parameters for Pentacam measurements should be regarded for proper clinical interpretation in children.

The effect of optical correction on refractive development in children with accommodative esotropia.

PURPOSE: To compare the effects of partial or full hyperopic optical correction on refractive development in children with accommodative esotropia. METHODS: Children with accommodative esotropia and hyperopia >3 D were enrolled in this prospective, nonrandomized study. All children underwent an ophthalmologic examination, including refraction, keratometry, and axial length. Subjects were divided into either full- or partial-correction groups according to their tolerance of the full hyperopic correction. Routine follow-up examinations were performed for at least 3 years. The main outcome measure was cycloplegic spherical equivalent at the end of the study period. RESULTS: A total of 120 children were enrolled. The mean cycloplegic spherical equivalent, corneal radius, and axial length were significantly (p < 0.05) different between the first and last visits in both groups. However, when all the measurements were adjusted for the age difference between groups, only the difference in axial length between the first and last visits was statistically significant (p < 0.05). Partial or full optical correction in age-adjusted cohorts with accommodative esotropia did not result in a significant change in refraction, keratometry, or axial length between the first and last visits. CONCLUSIONS: Partial or full optical correction of hyperopia had similar effects on refractive development of the eye in children with accommodative esotropia. Treatment of accommodative esotropia in children older than age 5 did not appear to impair refractive development.

Accommodative esotropia following surgical treatment of infantile esotropia: frequency and risk factors.

PURPOSE: We aimed to examine the frequency of and risk factors for the development of accommodative esotropia following surgical treatment for infantile esotropia. METHODS: A total of 29 children were recruited. Potential risk factors for the development of accommodative esotropia included: sex; angle of deviation at initial and final visits; cycloplegic refractive error at initial and final visits; increase in hyperopia; amblyopia; amblyopia treatment; age at surgical treatment; pre- and postoperative latent nystagmus; dissociated vertical deviation or inferior oblique muscle overaction; additional surgical procedures; unstable alignment, and binocular sensory status. RESULTS: Overall, 14 (48.2%) of 29 children developed accommodative esotropia during the 36- to 132-month postoperative follow-up period. Twelve (85.7%) of the 14 patients developed refractive accommodative esotropia and two developed non-refractive accommodative esotropia. The onset of accommodative esotropia occurred at a mean of 8.8 months (range 6-24 months) after the initial surgical alignment. This corresponded to a mean age of onset for accommodative esotropia of 43.2 months. We determined that, among children with infantile esotropia, those who had hyperopia of > or = 3.0 D and increasing hyperopia after surgery and those who did not develop dissociated vertical deviation during the follow-up period were more likely to develop accommodative esotropia. CONCLUSIONS: Children who have the established risk factors should be followed closely for the development of accommodative esotropia. The treatment of these children with appropriate glasses may prevent the development of adverse effects of accommodative esotropia on sensory and motor functions.

Factors influencing stereoacuity in refractive accommodative esotropia.

BACKGROUND: We aimed to investigate factors that promote binocular sensory function in patients with refractive accommodative esotropia (RAE) who have successful optical alignment. METHODS: Charts of 64 patients with RAE were retrospectively reviewed. Clinical factors examined included onset age of RAE, duration of misalignment, history of misalignment in family members, amblyopia, amblyopia treatment, refractive error, anisometropia, ocular movement disorders, visual acuity level, and the presence of intermittent or constant misalignment after optical correction of the hyperopic refractive error. RESULTS: Thirty-two patients (50%) were able to see test figures on any plates of TNO test and were considered to have stereoscopic vision. Intermittent or constant misalignment detected at any visit was found to affect stereoacuity adversely in patients with RAE. INTERPRETATION: Despite successful opitical alignment, as many as 50% of patients with RAE had anomalous binocular sensory function. An intermittent or constant eye misalignment poses a risk for anomalous binocular vision. These finding could promote prompt and appropriate optical corrections in order to minimize the adverse effects of intermittent or constant eye misalignment on binocular sensory function in patients with RAE.

Could personality traits modify the response to uncorrected high hyperopia?

PURPOSE: We aimed to measure temperament and investigate personality in children with high hyperopia considering that these could modify the individual response to uncorrected high hyperopia. METHODS: Fifteen children (age range, 5 to 12 years) with orthotropia and ametropic amblyopia in the presence of uncorrected high hyperopia were identified (group 1). Among the children with refractive accommodative esotropia, 15 children (age range, 5 to 12 years) were enrolled to form group 2. We measured the temperament by using the Children's Behavior Questionnaire (CBQ) Short Form. The Children's Apperception Test (CAT-H) was also administered to all subjects. RESULTS: Regarding the temperament scales measured by CBQ, themes of discomfort, fear, and shyness were more dominant in group 2; high-intensity pleasure and smiling-laughter were dominant in group 1. However the difference was statistically significant only for fear scale (P = 0.045). CAT-H results revealed that aggression toward the parents was the most commonly encountered behavioral pattern in both groups. The children in group 1 were more likely to express passive-aggressive behavioral pattern. Obstinacy and anal period characteristics dominate in the children in group 2. Themes of narcissistic injury was more frequently expressed by these children. CONCLUSION: The temperament scales and personality traits could play a role in the modification of the individual response to uncorrected high hyperopia. This finding deserves more research in a larger study group.

Comparison of achromatic and blue-on-yellow perimetry in patients with resolved central serous chorioretinopathy.

Central serous chorioretinopathy (CSCR) is a disorder characterized by the serous detachment of the sensory retina in the posterior pole. Although CSCR usually resolves spontaneously, the patients may notice residual visual deficits, despite recovering normal visual acuity. The aim of this study is to compare the blue-on-yellow perimetric parameters with conventional automated perimetric parameters in the detection of visual deficits in patients with resolved CSCR. Eighteen patients who had spontaneous recovered from CSCR were enrolled this study. All subjects were examined twice with each type of perimetry. Wilcoxon test was used for statistical analysis. The achromatic perimetric mean deviation values were significantly higher in patients with CSCR than in the control group, while statistically a significant difference was determined for all of blue-on-yellow perimetric values. In conclusion the loss of central retinal sensitivity remains after resolution of the CSCR even if the visual acuity has recovered to normal. Blue-on-yellow perimetry is more sensitive than achromatic perimetry to reveal this central sensitivity loss.

Orbital cellulitis after strabismus surgery.

Serious infection is uncommon after eye muscle surgery. Orbital cellulitis is a rarely reported but is potentially vision- and life-threatening complication after strabismus surgery. In this report, we describe a case of unilateral orbital cellulitis after strabismus surgery for sensory exotropia in a healthy adolescent boy.

Evaluation of the effects of radiotherapy to the chiasm and optic nerve by visual psychophysical and electrophysiologic tests in nasopharyngeal carcinoma.

PURPOSE: To evaluate the effects of high-dose radiotherapy (RT) to the chiasm and optic nerves in locally advanced nasopharyngeal carcinoma patients by visual psychophysical and electrophysiologic tests. METHODS AND MATERIALS: A series of visual tests, including visual evoked potentials (VEPs), contrast sensitivity, and visual field and visual acuity tests, were administered to 27 patients with locally advanced (T4) nasopharyngeal carcinoma who had undergone RT to high doses 6 to 74 months previously. As a control group, the same tests were administered to 40 unirradiated patients who had been referred to the ophthalmology department for any reason. RESULTS: The median values of VEP latency, VEP amplitude, and contrast sensitivity and the rate of visual field defect were significantly worse in the RT group (p = 0.06, p <0.001, p <0.001, and p = 0.005, respectively). No dose-response relationship was found in any tests when 50 Gy was the cutoff value. However, a positive correlation between the interval after RT and VEP latency (r = 0.406, p = 0.003) and a negative correlation between the interval and contrast sensitivity (r = -0.499, p <0.001) was noted; no correlation could be established regarding VEP amplitude and the interval after RT. CONCLUSION: Radiation-induced injury to the anterior visual pathways could result in an increase in VEP latency and a decrease in VEP amplitude and contrast sensitivity. This injury seems to be a continuous process developing with time.

Retroequatorial recession of horizontal recti with loop suture in the treatment of congenital nystagmus.

PURPOSE: The authors wished to evaluate the effectiveness and safety of retroequatorial recession of all four horizontal recti using loop sutures for the treatment of congenital nystagmus SUBJECTS AND METHODS: Twelve patients with congenital nystagmus were enrolled in this prospective study. All patients underwent retroequatorial recession of horizontal recti with loop sutures. All recti were recessed 8 mm measuring from the insertion, then the amount of loop suture was determined according to the preoperative ocular alignment of the patients. Electronystagmographic recordings were made in every patient preoperatively and postoperatively as well as an ophthalmological examination. The follow-up period ranged from 6 to 26 months. RESULTS: All four horizontal recti were recessed 9 to 12 mm including the loop suture (range 1-4 mm). Compared to preoperative values, postoperative amplitude and intensity of nystagmus decreased statistically significantly in all patients (p = 0.002). The postoperative decrease in the frequency of nystagmus was not statistically significant (p = 0.173). Improvement of both distance and near visual acuity was achieved in 10 patients. Five of seven patients who had ocular misalignment preoperatively were aligned within 10 PD postoperatively. Improvement in head posture was seen in two of three patients. The authors determined that the improvement in the nystagmus characteristics was most prominent in the immediate postoperative period. CONCLUSION: Retroequatorial recession of all four horizontal recti using loop sutures is a safe and effective procedure for the management of congenital nystagmus.

Blue-on-yellow perimetry versus achromatic perimetry in type 1 diabetes patients without retinopathy.

In this study, we compared the blue-on-yellow perimetric parameters with conventional automated static threshold perimetric parameters in the detection of psychophysical abnormality in patients with type 1 diabetes mellitus (DM) without diabetic retinopathy. Forty-three patients with type 1 DM without diabetic retinopathy were included this study. Thirty subjects served as age-matched control group. Blue-on yellow perimetry was performed and the results compared to white-on-white perimetry. The values of mean deviation by blue-on-yellow perimetry in the diabetic group were significantly higher than in the control group (P=0.0001). The indices of short fluctuation, pattern standard deviation, corrected pattern standard deviation and foveal sensitivity which all relate to localized depression in sensitivity were similar in both groups. The achromatic perimetric parameters were not different between the groups. We conclude that the short-wavelength-sensitive cones are vulnerable to damage from hyperglycemia and this influence can be detected early by blue-on-yellow perimetry in diabetic patients without retinopathy.

Oculometric features of hyperopia in children with accommodative refractive esotropia.

PURPOSE: To determine the nature of hyperopia in children with accommodative refractive esotropia (ARE) by evaluating the relationships between corneal radius (CR), axial length (AL), age and equivalent spherical refraction (SEQ). METHODS: A total of 112 children with ARE were included in the study. The children underwent an overall ophthalmic examination including cycloplegic refraction, keratometry and ultrasonic AL measurement. RESULTS: Statistical analysis revealed a strong relationship between AL and SEQ (p < 0.001). A significant correlation was also found between AL and CR (p < 0.001). The relationship between AL and age was weak but statistically significant (p = 0.02). Multiple regression analysis, using SEQ as the dependent variable and CR, AL and age as independent variables, revealed that AL accounts for 43.5% of the variance, and the combination of CR and AL accounts for 60.9% of the variance. CONCLUSION: Hyperopia is predominantly axial in nature in children with ARE. However, other refractive components are also involved in producing hyperopic refractive errors.

Negative social bias against children with strabismus.

PURPOSE: To determine whether the presence of noticeable strabismus creates a negative social bias against children. METHODS: Photographs of two boys and two girls were digitally altered to create photographs of the same child in orthotropic, esotropic and exotropic states. Elementary school teachers rated their perceptions of the children's personal characteristics (using a 10-item list of personal characteristics) based on their responses to these whole-face photographs. The participants were also asked to answer five questions related to the first impressions created by the photographs. RESULTS: Children with esotropia and exotropia were rated more negatively than orthotropic children on all 10 characteristics. Children with esotropia were rated more negatively than those with exotropia on most of these characteristics. CONCLUSIONS: Children with noticeable strabismus are viewed negatively. Hence, correction of strabismus may provide psychosocial benefits even when there is no hope of improving visual function.

The nature and origin of intraocular metallic foreign bodies appearing after phacoemulsification.

In order to evaluate the nature and origin of metallic foreign bodies embedded in the iris after uneventful phacoemulsification, we aimed to produce metallic fragments by applying ultrasound power with the same phaco machine and handpiece in an experimental model in vitro. In a glass bottle, we used linear phaco power of 100% continuously for 5 min first with a new phaco tip and then with a used tip. Afterwards, the fluid in the bottle was filtered through a Millipore filter. The remains on the filter were studied by scanning electron microscopy (SEM) and microprobe. Small particles remained on the filter which was used for the new tip. Microprobe microanalysis showed that these particles were mainly titanium, the same as the phaco tip. SEM of both the new and the used tips showed small fragments on the exterior surface and lumen. Intraocular metallic foreign bodies after phacoemulsification are likely to be shaken loose from the phaco tip. Although it is mostly agreed that these fragments are well tolerated, their overall effect remains to be evaluated in the long term.

Recession of the inferior rectus muscle under topical anesthesia in thyroid ophthalmopathy.

PURPOSE: To evaluate the results of inferior rectus muscle recession with adjustable loop suture under topical anesthesia for vertical deviations secondary to thyroid ophthalmopathy. PATIENTS AND METHODS: Five patients with a vertical deviation greater than 15 PD and severe limitation of upgaze were enrolled in the study. Before proceeding with corrective strabismus surgery, we waited at least 6 months after stabilization of ocular alignment and normalization of thyroid chemistries. All patients underwent inferior rectus muscle recession with adjustable loop suture under topical anesthesia. The postsurgical follow-up was at least 12 months. RESULTS: Preoperatively, the mean vertical deviation was 24 PD. At 1 year postoperatively, it had decreased to 2.4 PD. Two patients were orthotropic and 3 patients had residual hypotropia ranging from 2 to 6 PD. The limitation of upgaze was relieved significantly in the postoperative period. Two patients had minimal limitation of downgaze, but none complained of diplopia in the primary or reading positions. Surgery did not trigger a flare-up of orbital inflammation in the early postoperative period. CONCLUSION: We advocate that recession of the inferior rectus muscle with adjustable loop suture under topical anesthesia is safe and effective in patients with thyroid ophthalmopathy.