Retinal Thickness and Its Interocular Asymmetry Between Parkinson’s Disease and Drug-Induced Parkinsonism

Background@#Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging.Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson’s disease (PD). @*Methods@#We investigated 97 de novo PD patients and 27 DIP patients using OCT and [ 18 F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specificon-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. @*Results@#No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all Pvalues > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). @*Conclusion@#Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

Motor Asymmetry and Interocular Retinal Thickness in Parkinson's Disease

Background@#To analyze the relationship between interocular difference of retinal thickness and motor asymmetry in Parkinson's disease (PD). @*Methods@#Prospective case-control series analyzed 62 eyes of 31 patients with PD and 62 eyes of 31 age- and sex-matched control. Ophthalmologic examinations including optical coherence tomography (OCT) scans were performed in both groups, and in the patients with PD, motor function was evaluated on the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) to determine the clinically more affected side. Peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) were measured in both eyes, after which the interocular asymmetry of the OCT parameters was determined. Additionally, the more and less affected sides of the UPDRS-III were evaluated using Symmetric index. @*Results@#The average and quadrant pRNFLT and mRT values between the two groups were not different, but the interocular asymmetry of the average mRT and asymmetry index of retinal thickness (AIRT) of temporal mRT were significantly higher in the PD patients than in the controls (P = 0.026 and 0.044). The sum of UPDRS-III showed a discrepancy between the more and less affected sides (P = 0.002); the calculated Symmetric index was 0.21 ± 0.19, which suggested asymmetric motor symptoms. The Symmetric index of UPDRS-III showed significant relations for interocular asymmetry of superior mRT and AIRT of average mRT (P = 0.001 and 0.008). @*Conclusion@#In the PD patients, the interocular asymmetry of mRT was larger than in the controls, and the motor symptoms were asymmetric. Additionally, the interocular asymmetry of mRT showed a significant correlation with motor-symptom laterality.

Motor Asymmetry and Interocular Retinal Thickness in Parkinson's Disease

Background@#To analyze the relationship between interocular difference of retinal thickness and motor asymmetry in Parkinson's disease (PD). @*Methods@#Prospective case-control series analyzed 62 eyes of 31 patients with PD and 62 eyes of 31 age- and sex-matched control. Ophthalmologic examinations including optical coherence tomography (OCT) scans were performed in both groups, and in the patients with PD, motor function was evaluated on the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) to determine the clinically more affected side. Peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) were measured in both eyes, after which the interocular asymmetry of the OCT parameters was determined. Additionally, the more and less affected sides of the UPDRS-III were evaluated using Symmetric index. @*Results@#The average and quadrant pRNFLT and mRT values between the two groups were not different, but the interocular asymmetry of the average mRT and asymmetry index of retinal thickness (AIRT) of temporal mRT were significantly higher in the PD patients than in the controls (P = 0.026 and 0.044). The sum of UPDRS-III showed a discrepancy between the more and less affected sides (P = 0.002); the calculated Symmetric index was 0.21 ± 0.19, which suggested asymmetric motor symptoms. The Symmetric index of UPDRS-III showed significant relations for interocular asymmetry of superior mRT and AIRT of average mRT (P = 0.001 and 0.008). @*Conclusion@#In the PD patients, the interocular asymmetry of mRT was larger than in the controls, and the motor symptoms were asymmetric. Additionally, the interocular asymmetry of mRT showed a significant correlation with motor-symptom laterality.

Effect of Phacoemulsification on Intraocular Pressure in Healthy Subjects and Glaucoma Patients

BACKGROUND: We investigated how cataract surgery might influence long-term intraocular pressure (IOP) change in both healthy subjects and glaucoma patients. METHODS: A retrospective analysis of patients who had had clear corneal phacoemulsification with a minimum of 12 months of follow up was performed. Glaucoma patients with medically controlled open-angle glaucoma and healthy subjects with no glaucoma were included in the analysis. The change of IOP after phacoemulsification and factors associated with postoperative IOP change were investigated. RESULTS: In total, 754 eyes of 754 patients, specifically 106 patients with glaucoma and 648 patients with no glaucoma (i.e., healthy subjects) were enrolled. The phacoemulsification effected a reduction of IOP: 1.03 ± 3.72 mmHg in healthy subjects and 1.08 ± 3.79 mmHg in glaucoma patients at postoperative 1 year (P = 0.656). There were negative coefficients of IOP until 1 year of follow up (all P < 0.001), but the IOP change gradually showed a less steeply decreasing slope (correlation coefficient: −0.993), compared with those for 1 week and 1 month of follow up (correlation coefficients: −1.893 and −1.540, respectively). In the multivariate analysis, age and preoperative IOP showed significant associations with postoperative IOP change (regression coefficients: −0.034 and 0.419 respectively, all P < 0.001). CONCLUSION: Phacoemulsification resulted in IOP reduction, which effect regressed in healthy subjects and glaucoma patients over the course of long-term follow up. Therefore, long-term monitoring of IOP change is needed. In cases of higher preoperative IOP and young patients, phacoemulsification alone is a reliable option for IOP control.

Safety of Using Matrix Metalloproteinase Inhibitor in Experimental Glaucoma Filtration Surgery

We evaluated the safety of matrix metalloproteinase (MMP) inhibitor in experimental glaucoma filtration surgery in an animal model. Fifteen New Zealand white rabbits underwent an experimental trabeculectomy and were randomly allocated into 3 groups according to the adjuvant agent: no treatment group (n = 5), 0.02% mitomycin C (MMC) soaking group (n = 5), and MMP inhibitor (ilomastat) subconjunctival injection group (n = 5). Slit lamp examination with Seidel testing, pachymetry, and specular microscopy was performed preoperatively and postoperatively. The conjunctiva and ciliary body toxicity were evaluated with scores according to the pathologic grading systems. Electron microscopy was used to examine the structural changes in cornea, conjunctiva, and ciliary body. In the ilomastat-treated group, there was no statistically significant change in central corneal thickness preoperatively and at 28 days postoperatively (P = 0.655). There were also no significant changes in specular microscopy findings over the duration of the study in the ilomastat-treated group. The conjunctival toxicity score was 1 in the control group, 1.5 in the ilomastat-treated group, and 2 in the MMC-treated group. When assessing ciliary body toxicity scores, the ilomastat-treated group score was 0.5 and the MMC-treated group score was 1.5. Transmission electron microscopy did not show structural changes in the cornea and ciliary body whereas the structural changes were noticed in MMC group. A single subconjunctival injection of MMP inhibitor during the experimental trabeculectomy showed a less toxic affect in the rabbit cornea, conjunctiva, and ciliary body compared to MMC.

Depth and Area of Retinal Nerve Fiber Layer Damage and Visual Field Correlation Analysis

PURPOSE: To evaluate the relationship between the structural damage as assessed by time-domain optical coherence tomography (OCT) and functional changes in glaucoma. METHODS: In total, 190 patients with normal tension glaucoma or primary open angle glaucoma were included in this study. The thickness of retinal nerve fiber layer (RNFL) around the optic disc and the area of RNFL defect were determined using OCT scans. The relationships between the RNFL thickness or area of the defect and visual field (VF) indices were assessed using the Lowess function, regression analysis and partial Spearman correlation. The differences between these associations depending on the stage of VF damage were further analyzed. Age, optic disc size, refraction, central corneal thickness and the presence of systemic disease were corrected for in order to exclude confounding factors. RESULTS: A logarithmic scale of RNFL thickness showed a negative linear relationship with VF indices. The area of the RNFL defect showed a weak correlation with the pattern of standard deviation, whereas the remnant RNFL thickness was moderately correlated with the pattern of standard deviation (partial Spearman correlation coefficient, 0.39, -0.47, respectively; p < 0.0001). Many outliers were detected in the Lowess-plotted graphs. Multiplication of the area and the inverted RNFL thickness showed a moderately correlated logarithmic relationship with the VF indices (partial Spearman correlation coefficient, 0.46; 95% confidence interval, 0.34 to 0.57; p < 0.0001). In the severe stage of VF damage, correlation between the area of the RNFL defect and mean deviation was significantly greater than in other stages (partial Spearman correlation coefficient, -0.66; p = 0.02). CONCLUSIONS: The thickness of the RNFL had a negative logarithmic correlation with the VF indices and was more relevant to the VF indices than the area of the RNFL defect, as measured by OCT.

The Relations Between Progression of Peripapillary Chorioretinal Atrophy and Progression of Normal Tension Glaucoma

PURPOSE: To evaluate the relations between progression of glaucoma in visual field and peripapillary area change in normal tension glaucoma (NTG). METHODS: We respectively evaluated 66 patients (66 eyes) with normal tension glaucoma; these patients were classified as progressive glaucoma group and non-progressive glaucoma group by visual field test. Interobserver and intraobserver agreement was evaluated for qualitative assessment. Zone beta change was measured by Image J (National Institute of Health, Bethesda, USA) by two methods. One method used paired t-test and the other method used CV (correlation of variation) to define significant progression of zone beta. RESULTS: 46 patients (46 eyes) were classified as progressive glaucoma and 20 patients (20 eyes) were classified as non-progressive glaucoma. There was no statistically significant different change of zone beta between two groups and there were no changes of zone beta over coefficient of variation (CV). CONCLUSIONS: The measurement of change of zone beta seems to be of no use in recognition of progression in normal tension glaucoma.

Comparative Study of Encapsulated Blebs Following Ahmed Glaucoma Valve Implantation and Trabeculectomy with Mitomycin-C

PURPOSE: To compare the histopathologic and morphologic findings of encapsulated blebs following Ahmed glaucoma valve implantation and primary standard trabeculectomy with mitomycin-C. METHODS: We reviewed the records of patients with otherwise uncontrollable glaucoma who had undergone Ahmed glaucoma valve implantation or trabeculectomy with mitomycin-C. Five eyes that underwent Ahmed valve implantation and three eyes that underwent trabeculectomy needed surgical revision of the initial surgery due to encapsulated bleb development with total loss of function. The surgically removed encapsulated blebs were analyzed macroscopically and microscopically. RESULTS: Removal of the encapsulated bleb was performed at a mean follow-up time of 26.6 +/- 19.4 weeks in the Ahmed valve implantation group and 12.0 +/- 11.4 weeks in the trabeculectomy group. The fibrotic wall of the encapsulated blebs had an overall thickness of 2.48 +/- 0.42 mm in the Ahmed valve implantation group and 1.62 +/- 0.37 mm in the trabeculectomy group. Macroscopically, the coconut flesh-like smooth surface was split into two layers, and the wall of the capsule was thicker in the Ahmed valve implantation group than in the trabeculectomy group. Histopathologically, the fibrotic capsule was composed of an inner fibrodegenerative layer and an outer fibrovascular layer, and there were no histopathological differences between the two groups. CONCLUSIONS: The fibrotic capsule wall was thicker in the Ahmed valve group, but there were no differences in histological findings between the two groups.

Comparision of Primary Vascular Dysregulation for Unilateral and Bilateral Eye Involvement in Normal Tension Glaucoma

PURPOSE: To compare the clinical symptoms and signs of primary vascular dysregulation (PVD) for unilateral and bilateral eye involvement in normal tension glaucoma (NTG). METHODS: The authors administered a questionnaire to assess PVD in patients with NTG. The answers to the 10-item questionnaire (cold hands, migraine, sleep latency, thirst, hypotension, orthostatic hypotension, emotional stress, drug sensitivity, vertigo, and systemic vasospasm) were compared between patients with unilateral involved NTG and bilateral involved NTG (N=61). The groups were classified again according to age (criteria: 55 years), sex, and mean deviation via standard automated perimetry (criteria: -6 dB). RESULTS: The answers to the questionnaire between patients with unilateral involved NTG and bilateral involved NTG were not different at the level of statistical significance. In groups classified according to age, sex, and mean deviation, none of the answers to the questionnaire were different at the level of statistical significance between the groups. CONCLUSIONS: Clinical symptoms and signs of PVD were not different between patients with unilateral or bilateral eye involvement in NTG. Systemic vascular factors may not be considered different between unilateral and bilateral eye involvement in NTG.

Comparison of Primary Vascular Dysregulation in Normal Tension Glaucoma and Primary Open Angle Glaucoma

PURPOSE: To evaluate the clinical symptoms or signs of primary vascular dysregulation (PVD) in patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG). METHODS: From June 2008 to June 2009, we administered questionnaires to patients with glaucoma. The questionnaire was composed of 11 items, and the questionnaire results were compared between patients with NTG and POAG. NTG patients were subdivided by age(criterion: 55 years) and perimetric mean deviation (criterion: -6dB). RESULTS: We detected a significant increase in hypotension (p=0.036) in NTG patients (n=133), compared to POAG patients (n=68). Migraines and emotional stress were more frequent in younger patients (55 years) with NTG (27.5%, 42.9%, p=0001). The frequency of drug sensitivity and systemic vasospasm is higher in older patients with NTG (28.6%, 17.4%) than younger patients with NTG (12.9%, 4.9%) but the rate of systemic vasospasm is much higher in younger patients, compared to the prevalence in the general Korean population. In patients with moderate and advanced NTG, hypotension is highly prevalent (p=0.018). CONCLUSIONS: Hypotension is a greater risk factor for NTG than for POAG. Indeed, vascular factors may be correlated with NTG, especially in younger patients with moderate, advanced visual field defects.

Longitudinal Analysis of Retinal Nerve Fiber Layer Thickness With GDx-VCC in Glaucoma Suspect

PURPOSE: The changes of retinal nerve fiber layer thickness with GDx-VCC were analyzed to assess the use of this instrument for longitudinal follow-up of retinal nerve fiber layers. METHODS: From July 2004 to July 2007, patients suspected of glaucoma were measured with GDx-VCC at baseline and measurements were repeated at a minimum interval of 12 months. The medical records of 150 patients were reviewed and 42 patients that showed glaucomatous visual field progression in 36 months were classified into a "progression group" and 108 patients with no visual field loss were classified into a "nonprogression group". RESULTS: In the nonprogression group, the temporal superior-nasal-inferior-temporal (TSNIT) average and theinferior average showed statistically significant changes for the follow up periods. However, in theprogression group, there were no parameters with significant changes even though glaucomatous visual field loss was found. The visual field progressed at a rate of 0.1dB/year in the progression group but the relationship between MD, PSD and GDx-VCC parameters could not be established. CONCLUSIONS: GDx-VCC may not be sufficient for longitudinal assessment of the RNFL, especially during the early glaucomatous visual field changes. The progression of glaucoma only with GDx-VCC should be cautiously evaluated, and confirmation with the visual field which elucidates early glaucomatous changes is necessary. Further study is needed before GDx-VCC can be recommended as the instrument for longitudinal assessment.

Delayed Epithelial Ingrowth Caused by Viral Conjunctivitis after LASIK

To report a patient who presented with epithelial ingrowth caused by viral keratoconjunctivitis 3 months after LASIK surgery. A 41-year-old man presented with decreased visual acuity in the right eye, which had developed about 3 weeks before. He had undergone LASIK surgery 3 months prior without complications. Two months after the surgery, he was treated for viral conjunctivitis. During the treatment period, filamentary keratitis developed, and a therapeutic bandage contact lens was applied for 2 weeks. Upon presentation, examination revealed a corrected visual acuity of 20/100 and irregular epithelial sheets under the edematous flap. The flap was lifted, and the in-grown epithelium was removed. The flap was repositioned with double continuous 10-0 nylon sutures. Post-operatively, the patient developed a mild diffuse lamellar keratitis that resolved rapidly with topical corticosteroid treatment. At 2 months, the corrected visual acuity was 20/20 without interface opacities. As the patient showed no complications prior to viral conjunctivitis, we suspect that the viral infection caused edema of the corneal flap, which caused epithelial ingrowth under the flap. Patients who have viral conjunctivitis after LASIK surgery should be examined carefully and managed with consideration of flap complications.

The Calretinin Immunoreactive Ganglion Cell Postsynaptic to the ON-Cholinergic Amacrine Cell in the Guinea Pig

PURPOSE: To demonstrate the characterization calretinin-immunoreactive displaced amacrine cells in the ganglion cell layer using immunohistochemistry and electron microscopy. METHODS: For immunohistochemistry, sections from guinea pig retina were incubated with mouse monoclonal antibody directed against calretinin. For double label studies, sections were incuated in mixture of mouse monoclonal anti-calretinin or rabbit polyclonal anti-calretinin with following antibodies: goat polyclonal anti-ChAT, rabbit polyclonal anti-GABA, mouse monoclonal anti-GABAA receptor alpha1, beta2/3. Sections were analyzed using Bio-rad Radiance Plus confocal scanning microscope. Stained sections from three guinea pig were observed with transmission electron microscope. RESULTS: Calretinin immunoreactivity was present in displaced amacrine cells and ganglion cells gaving rise to processes ramified in the inner part of the inner plexiform layer in stratum 4. The same stratum was also occupied by the dendrites of ON-cholinergic amacrine cells. Double-labeling demonstrated that dendrites and cell bodies of displaced amacrine cells colocalized with ON-cholinergic amacrine cells and dendrites of ganglion cells directly overlapped with dendrites of ON-cholinergic amacrine cells. The synaptic connectivity was identified by electron microscopy. Ganglion cell dendrites received synaptic input from ON-cholinergic amacrine cell. GABAA receptor beta2/3 subunit bands cofaciculates the dendrites of displaced amacrine cell and ganglion cell that are juxtapose to the alpha1 subunit of GABAA receptor. CONCLUSIONS: These results indicate that ON-cholinergic amacrine cells modulate calretinin-labeled ganglion cell via GABAA receptor beta2/3 in the guinea pig retina.

Clinical Manifestations of Presumed Sterile Endophthalmitis After Intravitreal Triamcinolone Injection

PURPOSE: To evaluate the distinguishing characteristics that may assist in the clinical diagnosis of sterile endophthalmitis from intravitreal triamcinolone injection. METHODS: From January 2005 to June 2006, the medical records of 163 eyes that received intravitreal triamcinolone injection were reviewed. In 5 eyes of 5 patients who complained of decreasing vision and mild ocular pain within three days after injection, slit lamp bimicroscopy revealed hypopyon, anterior chamber reaction, and vitritis. We analyzed clinical pictures retrospectively. RESULTS: Intravitreal triamcinolone injections were performed for diabetic macular edema in 4 patients and for panuveitis in 1 patient with Behcet's disease. Pseudophakia was found in all five eyes. Inflammations in three eyes resolved with topical and oral antibiotics within 13 days, and the other two patients were treated with a vitreous culture and intravitreal antibiotic injection. However, vitreous tap showed no evidence of endophthalmitis, and inflammation resolved within the same period. CONCLUSIONS: Presumed sterile endophthalmitis presents within 3 days after intravitreal triamcinolone injection and may be accompanied by decreased vision and ocular discomfort, although it is characterized by no distinct ocular pain. The symptoms and ocular inflammation resolved quickly within 13 days with a favorable visual outcome. Inflammations in three eyes resolved without surgical intervention, so it may be necessary to closely observe clinical manifestations before assuming that the eye is suffering from infectious endophthalmitis.

Change in Optic Nerve Head Topography in Progression of Early Glaucoma

PURPOSE: To investigate the clinical manifestation and the structural optic disc changes according to the development of reproducible visual field defects in a group of preperimetric patients converting to early glaucoma. METHODS: Standard automated perimetry (Humphrey Field Analyzer) was performed every six months in 294 preperimetric patients. Each subject was classified as either converter or non-converter according to glaucomatous visual field changes, and the clinical manifestations were analyzed retrospectively. Sequential optic disc images were obtained using the TopSS scanning laser ophthalmoscope (TopSS(TM)) and optic disc parameters were measured to determine if any change had occurred. RESULTS: A total of 44 eyes from 44 subjects (14.9%) in 294 patients subsequently developed early glaucomatous field loss (converters). The progression rate of visual field defect is 0.43dB/year. In respect to age, sex, refractive error, and diabetes mellitus, no significant differences were observed. Elevated IOP, hypertension, and family history of glaucoma were detected more frequently in the converter group than in the non-converter group. Among TopSS parameters, cup-to-disc ratio, effective area, volume above, maximum slope, and neuroretinal rim area showed statistically significant change. Changes of the neuroretinal rim were prominent in superior and inferior sectors. CONCLUSIONS: Among TopSS parameters, cup-to-disc ratio, effective area, volume above, and neuroretinal rim are useful in detecting the progression of glaucoma. Furthermore, neuroretinal rim changes in each sector may provide clinically relevant information in detecting and monitoring the progression of glaucoma.

Change in Optic Nerve Head Topography in Progression of Early Glaucoma

PURPOSE: To investigate the clinical manifestation and the structural optic disc changes according to the development of reproducible visual field defects in a group of preperimetric patients converting to early glaucoma. METHODS: Standard automated perimetry (Humphrey Field Analyzer) was performed every six months in 294 preperimetric patients. Each subject was classified as either converter or non-converter according to glaucomatous visual field changes, and the clinical manifestations were analyzed retrospectively. Sequential optic disc images were obtained using the TopSS scanning laser ophthalmoscope (TopSS(TM)) and optic disc parameters were measured to determine if any change had occurred. RESULTS: A total of 44 eyes from 44 subjects (14.9%) in 294 patients subsequently developed early glaucomatous field loss (converters). The progression rate of visual field defect is 0.43dB/year. In respect to age, sex, refractive error, and diabetes mellitus, no significant differences were observed. Elevated IOP, hypertension, and family history of glaucoma were detected more frequently in the converter group than in the non-converter group. Among TopSS parameters, cup-to-disc ratio, effective area, volume above, maximum slope, and neuroretinal rim area showed statistically significant change. Changes of the neuroretinal rim were prominent in superior and inferior sectors. CONCLUSIONS: Among TopSS parameters, cup-to-disc ratio, effective area, volume above, and neuroretinal rim are useful in detecting the progression of glaucoma. Furthermore, neuroretinal rim changes in each sector may provide clinically relevant information in detecting and monitoring the progression of glaucoma.