Investigating the factors affecting myopia in retinopathy of prematurity after laser treatment.

BACKGROUND: We investigated the effect of the number of laser shots applied on the myopic variables to elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes. METHODS: A total of 33 eyes of 17 infants with ROP who underwent laser treatment were included in the analysis. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age-matched control group without ROP was prepared and ocular structural parameters were compared. RESULTS: Although there was no statistical difference in axial length (AL) between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p < 0.001). SE was associated with AL, corneal refraction (CR), and crystalline lens power (CLP) in the ROP group. Of these three factors (AL, CR, and CLP), CLP and the number of laser shots applied were significantly correlated (p = 0.003); however, no correlations were observed between the number of laser shots and AL or CR (p = 0.15 and 0.10, respectively). Very similar tendency was observed in the analysis of the difference between right and left eyes in each child. CONCLUSIONS: In laser-treated ROP eyes, AL, CR, and CLP were related to the degree of myopia. Moreover, the number of shots applied also affected the myopic status in laser-treated ROP eyes. Among AL, CR, and CLP, only CLP was correlated with the laser shots applied.

Surgical Treatment for a Full-Thickness Macular Hole That Developed on a Large Drusenoid Pigment Epithelial Detachment.

Full-thickness macular hole (FTMH) and age-related macular degeneration (AMD) can affect the same eyes in the older population. Previously reported phenotypes of AMD concurrent with FTMH include early/intermediate AMD and serous pigment epithelial detachment (PED). A 68-year-old woman presented to our clinic with decreased vision due to a cataract and a large drusenoid PED in both eyes. After ruling out choroidal neovascularization, she underwent cataract surgery. Three days after the cataract surgery, an FTMH was found in the left eye. Although the FTMH was not closed after the initial pars plana vitrectomy (PPV) with the inner limiting membrane (ILM) peeling and air tamponade, it was closed after reoperation with additional ILM peeling, retinal massage, and SF6 gas tamponade. Best-corrected visual acuity (BCVA) was improved from 20/60 before the first PPV to 20/40 at six months after the reoperation. Some large soft drusen in the macula were fused after surgeries in the operated eye, but not in the fellow eye. An FTMH concurrent with a large drusenoid PED is rare. It can be closed surgically, and postoperative visual function can improve.

Fovea-Sparing as Opposed to Total Peeling of Internal Limiting Membrane for Myopic Foveoschisis: A Systematic Review and Meta-analysis.

TOPIC: The effectiveness of fovea-sparing (FS) peeling of internal limiting membrane (ILM) to treat myopic foveoschisis (MF) has not been understood fully. The present meta-analysis aimed to compare postoperative visual and anatomic outcomes between FS peeling and total peeling (TP) of ILM in pars plana vitrectomy for the treatment of MF. CLINICAL RELEVANCE: Postoperative macular hole (MH) development is not uncommon and is a serious complication after surgery for MF, with poor visual prognosis. Fovea-sparing peeling of ILM is expected to reduce the risk of postoperative MH; however, no statistically significant evidence exists to prove this hypothesis. In addition, its effect on postoperative visual acuity has not been clear. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were reviewed systematically, and studies that compared FS with total ILM peeling in MF surgery were retrieved. The protocol was registered in International Prospective Register of Systematic Reviews (identifier, CRD42020201675). Primary outcome measures were the postoperative best-corrected visual acuity (BCVA) and frequency of postoperative MH development. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Eight studies with 300 eyes from 289 patients were included. All studies were nonrandomized and observational. The postoperative BCVA was significantly better in eyes treated with FS (mean difference [MD], -0.15 logarithm of the minimum angle of resolution [logMAR]; 95% confidence interval [CI], -0.24 to -0.05 logMAR; P = 0.002). The risk of postoperative MH was significantly lower in the FS group (odds ratio, 0.19; 95% CI, 0.06-0.56; P = 0.003). No significant difference was found in postoperative central foveal thickness (MD, 12.59 µm; 95% CI, -2.8 to 28.0 µm; P = 0.11). The certainty of evidence regarding lower frequency of postoperative MH after FS peeling was considered moderate, whereas the certainty regarding better postoperative BCVA after FS peeling was judged to be low. DISCUSSION: Fovea-sparing peeling may contribute to better visual acuity outcome and lower risk of postoperative MH development in eyes with MF.

Does the number of laser applications for ROP treatment influence the degree of myopia?

PURPOSE: To evaluate the relationship between the number of laser shots applied during laser photocoagulation treatment and the degree of myopia at 3 years in children with laser-treated retinopathy of prematurity (ROP). METHOD: A total of 68 eyes of 34 infants who had developed prethreshold ROP and were treated by diode laser therapy were included in the current study. Cycloplegic retinoscopic refraction testing was performed in the children at the age of 3 years, and the spherical equivalent (SE) was calculated for all the examined eyes. The number of laser shots that had been applied was compared between the eyes with and without high myopia (SE < - 5 diopters (D)). In addition, the relationship between the difference in the SE values between the two eyes in each infant and the difference in the number of laser shots applied between the two eyes was also analyzed. RESULTS: The number of laser shots applied was significantly higher for the eyes with high myopia than for those without high myopia (p = 0.0088), and the number of laser shots applied was significantly positively correlated with the degree of myopia (p < 0.001). A significant correlation was also observed between the differences in the SE values between the two eyes and the differences in the number of laser shots applied between the two eyes (p = 0.0013). CONCLUSION: The number of laser shots applied in photocoagulation treatment for ROP is significantly associated with the degree of myopia seen subsequently in the children.

Pathologic myopia: an overview of the current understanding and interventions.

Pathologic myopia is a major cause of low vision and blindness worldwide. Its social and economic burden has been demonstrated by epidemiological studies. There have been recent advances in the classification system for myopic maculopathy that enables clinicians to describe different types of lesions, including tessellated fundus, diffuse/patchy chorioretinal atrophy, macular atrophy, lacquer cracks, choroidal neovascularization (CNV), and Fuchs' spot, in a standardized format. From a therapeutic point of view, anti-vascular endothelial growth factor therapy has been established as first-line choice for myopic CNV. For myopic retinoschisis and macular holes with/without retinal detachment, pars plana vitrectomy has been generally accepted as an efficient strategy. Studies are being conducted to determine how to avoid the development of a postoperative macular hole and to improve the quality of vision after surgery. In recent years, studies have revealed preventive measures that can be taken against myopia progression, including low-dose atropine eyedrops and contact lens wearing with peripheral myopic defocusing.

Using flowchart for ophthalmic consultations in hospitalized patients with COVID-19.

Ocular complications of coronavirus disease 2019 (COVID-19) do not essentially cause serious visual loss. However, due to the characteristics of this disease, delays in diagnosis and treatment in hospitalized patients may leave them with serious visual impairment. If conjunctivitis is suspected, ophthalmological follow-up is needless because it is expected spontaneous healing. Diplopia is often complicated for extra-ocular neurological findings and need neurological consults. Ophthalmologists should be consulted for ocular surface disease, high intraocular pressure, and ocular inflammation that may cause visual loss if patients complain of blurred vision, visual loss, and ocular pain. The problem is unconscious patients with risk of developing high intraocular pressure or keratitis. An ophthalmologist should be consulted as soon as possible if eye redness or pupil abnormalities appear in these patients. We developed a flowchart for ophthalmic consultations in hospitalized patients with COVID-19, for facilities where an ophthalmologist is not always present, and for third or fourth waves or, a pandemic of another infectious disease.

Rho-associated protein kinase inhibitor induced morphological changes in type VI collagen in the human trabecular meshwork.

AIMS: To investigate morphological changes in type VI collagen in the human trabecular meshwork associated with the rho kinase inhibitor ripasudil. METHODS: This cross-sectional study evaluated the effects of ripasudil eye drop administration (RA) or no ripasudil eye drop administration (NRA) in patients with primary open-angle glaucoma (POAG; age range 60-80 years) who underwent conventional outflow reconstruction between December 2015 and September 2016 at Tokai University Hachioji Hospital. The juxtacanalicular tissue was removed and imaged using transmission electron microscopy. Type VI collagen comprises cross-banded aggregates with transverse bands 30 nm apart repeating every 105 nm. The transverse bands are called the outer rod-like region (ORR) and the intervals are called the inner rod-like region (IRR). The waveform intensity in the type VI collagen was analysed in electron micrographs using Fourier transformation to detect the IRR and ORR borders. RESULTS: Ten eyes of 10 patients were included (n=5/group). The baseline characteristics did not differ significantly between groups. ORR width was significantly smaller in the RA group (37.85±3.43 nm) than in the NRA group (50.62±5.23 nm, p<0.05), whereas IRR width was significantly greater in the RA group (70.68±10.84 nm) than in the NRA group (58.19±5.34 nm, p<0.05). Morphological changes in the type VI collagen total width tended to correlate with the duration of ripasudil administration (r=0.9, p=0.08). CONCLUSIONS: Ripasudil administration in patients with POAG induced morphological changes in type VI collagen. Patients with POAG administered RA had a significantly smaller ORR width and a significantly greater IRR width than patients with POAG not administered RA.

Potential Utility of a 4K Consumer Camera for Surgical Education in Ophthalmology.

Purpose. We evaluated the potential utility of a cost-effective 4K consumer video system for surgical education in ophthalmology. Setting. Tokai University Hachioji Hospital, Tokyo, Japan. Design. Experimental study. Methods. The eyes that underwent cataract surgery, glaucoma surgery, vitreoretinal surgery, or oculoplastic surgery between February 2016 and April 2016 were recorded with 17.2 million pixels using a high-definition digital video camera (LUMIX DMC-GH4, Panasonic, Japan) and with 0.41 million pixels using a conventional analog video camera (MKC-501, Ikegami, Japan). Motion pictures of two cases for each surgery type were evaluated and classified as having poor, normal, or excellent visibility. Results. The 4K video system was easily installed by reading the instructions without technical expertise. The details of the surgical picture in the 4K system were highly improved over those of the conventional pictures, and the visual effects for surgical education were significantly improved. Motion pictures were stored for approximately 11 h with 512 GB SD memory. The total price of this system was USD 8000, which is a very low price compared with a commercial system. Conclusion. This 4K consumer camera was able to record and play back with high-definition surgical field visibility on the 4K monitor and is a low-cost, high-performing alternative for surgical facilities.

Goniosynechialysis and Repositioning of Intraocular Lens in a Case of Secondary Angle Closure Glaucoma.

PURPOSE: Implanting intraocular lens (IOL) in proper direction is important in cataract surgery to reduce the possibility of undesirable complications. We experienced a case who underwent vitrectomy combined with cataract surgery and developed secondary angle closure glaucoma caused by IOL misdirection. Goniosynechialysis (GSL) and repositioning of IOL successfully ameliorated the high intraocular pressure (IOP). CASE REPORT: A 64-year-old male with massive vitreous hemorrhage underwent vitrectomy combined with cataract surgery. In implanting IOL, posterior capsule was accidentally raptured, and we were obliged to implant IOL reversely in the ciliary sulcus. A month postoperatively, the capture of IOL by iris and the shallow anterior chamber with iris bombe formation led to the elevated IOP up to 60 mmHg. Laser iridotomy and maximum anti-glaucoma medications including oral carbon anhydrase inhibitor could not control IOP. Subsequently, we performed GSL and IOL repositioning to correct the lens direction and the IOP was successfully reduced to normal level. CONCLUSION: Reversely sulcus-implanted IOL should be repositioned to prevent secondary angle closure glaucoma.

A Case of Open-Angle Glaucoma Successfully Treated Using Canaloplasty.

OBJECTIVE: We report the case of a patient with open-angle glaucoma who underwent canaloplasty and subsequently maintained good intraocular pressure (IOP) control for the entire duration of the 4-year follow-up. SUBJECTS: The patient was a 68-year-old man who was diagnosed with open-angle glaucoma and uncontrollable IOP at the Tokai University Hachioji Hospital in January 2011. Visual field examination revealed an arcuate visual field defect in the left eye, but no visual field defect in the right eye. In order to lower the IOP, canaloplasty was performed on his left eye. RESULTS: There were no complications either during or after the surgery. The IOP values at 2 weeks, 1 month, 6 months, 1 year, 2 years, 3 years, and 4 years were, 13, 14, 18, 12, 10, 12, and 8 mmHg, respectively. No deteriorations in visual field or reductions in visual acuity were detected during this follow-up.There were no long-term complications such as cataract formation or exposure of the suture. Spectral domain optical coherence tomography showed that the trabecular meshwork was inwardly distended because of the intracanalicular suture in the affected eye. CONCLUSION: Canaloplasty can be a safe and effective surgical method for lowering the IOP in glaucoma patients.

Outcomes of Late-Onset Bleb-Related Endophthalmitis Treated with Pars Plana Vitrectomy.

Purpose. To investigate clinical results on bleb-related endophthalmitis (BRE) after trabeculectomy treated with pars plana vitrectomy (PPV) and to evaluate influence factors for visual prognosis. Methods. Investigating medical records retrospectively, BRE was defined as an endophthalmitis induced by bleb infection. A total of 2018 eyes of 1225 patients who had trabeculectomy between December 2000 and July 2013 were included in this study. Eleven eyes of 11 patients with BRE were performed with PPV. Results. The mean age was 56.6 years. The mean period between trabeculectomy and BRE onset was 7.4 years. The mean period from starting symptom to initiation of treatment for endophthalmitis (PSITE) was 2.3 days. Bleb leakages were observed in 7 eyes (64%). On culture examinations, highly pathogenic bacteria (HPB) were identified in 6 cases (55%). HPB infection was influence factors on visual disturbance (P = .0337). Number of HPB infections is significantly higher in poor visual outcome than without poor visual outcome (P = .0310). Conclusion. Visual prognosis of BRE treated by PPV is significantly better when the pathogenic bacteria are not HPB. Severe visual loss occurred with HPB infection even though patients had appropriate treatments. Physicians need to have careful consideration to prevent bleb infection after trabeculectomy with MMC.

Tear meniscus volume changes in dacryocystorhinostomy evaluated with quantitative measurement using anterior segment optical coherence tomography.

PURPOSE: To evaluate tear meniscus (TM) changes in external dacryocystorhinostomy (ex-DCR) with quantitative measurement of tear meniscus height (TMH), area (TMA), and volume (TMV) using anterior segment optical coherence tomography (AS-OCT). METHODS: Twenty-five eyes from 21 patients (11 males and 10 females) with primary acquired nasolacrimal duct obstruction (PANDO) who received ex-DCR from May 2010 to April 2011 were evaluated prospectively on their TMH, TMA, and TMV changes by AS-OCT. Measurements were performed before surgery (Pre) and 2 weeks (2W), 2 months (2M), and 6 months (6M) after surgery. Data were analyzed using Kruskal-Wallis test, Wilcoxon signed-rank test with Bonferroni adjustment, and Spearman's rank correlation coefficient. RESULTS: All patients had a good clinical course, and there were significant differences in the values of each TM parameter before and after surgery (P < 0.0001). The median values of TMH (mm) throughout the observation period were 0.707 (Pre), 0.334 (2W), 0.278 (2M), and 0.277 (6M). The TMA median values (mm(2)) were 0.1097 (Pre), 0.0483 (2W), 0.0255 (2M), and 0.0224 (6M). The TMV median values (mm(3)) were 0.7799 (Pre), 0.1614 (2W), 0.1071 (2M), and 0.1553 (6M). There were significant differences in TMH, TMA, and TMV reduction at each postoperative visit as compared to preoperative values (P < 0.001). In addition, TMH change 6 months after ex-DCR showed a significant positive correlation with age (r = 0.4434, P = 0.0264). CONCLUSIONS: The perioperative TM changes in ex-DCR can be evaluated noninvasively and quantitatively by using AS-OCT.

Predisposing factors for primary acquired nasolacrimal duct obstruction.

BACKGROUND: Pathological origin of primary acquired nasolacrimal duct obstruction (PANDO) is considered as inflammation of unknown causes; however, specific predisposing factors have not been fully addressed to date. METHODS: In an institutional setting, background factors of 45 patients with PANDO were compared to those in 67 control subjects. The control subjects were persons with senile cataract, representing the non-pathological general population. The evaluated background factors were inflammatory medical histories (infectious conjunctivitis and allergic conjunctivitis and/or rhinitis), previously reported factors (POAG and topical timolol), and a novel factor proposed in the current study (exposure to swimming pool). Data were extracted from the patients through interview based on a standardized questionnaire as well as from their clinical records. RESULTS: After adjustment for age and gender, a history of infectious conjunctivitis was more common in the PANDO group than in the control group (55.6 % vs 32.8 %, P = 0.0027), and regular attendance to indoor swimming pools was also more common in the PANDO group (33.3 % vs 0 %, P < 0.0001). Furthermore, when age- and gender- matched subjects were selected, a history of conjunctivitis and swimming pool exposure were independently associated with the development of PANDO (P = 0.022 and P < 0.0001 respectively). On the other hand, the frequencies of histories of POAG, topical timolol, and allergic conjunctivitis and/or rhinitis were similar between the two groups. CONCLUSIONS: Histories of infectious conjunctivitis and swimming pool exposure could be associated with the development of PANDO, although the pathogenesis of this condition has been considered as inflammation of unknown causes.

In vivo measurement of blood velocity in human major retinal vessels using the laser speckle method.

PURPOSE: To develop a simple, noninvasive method of determining blood velocity and flow through human retinal vessels (RVs), by using the laser speckle method and validating the results by bidirectional laser Doppler velocimetry (LDV). METHOD: The square blur rate (SBR), a quantitative blurring index of the laser speckle pattern that parallels the velocity of moving substances, obtained from blood flowing through glass capillary tubes (RV analogues), correlated with tube diameter, background reflectance and absorption, flow velocity, and the SBR obtained from blood flowing through underlying glass capillary tubes (choroidal vessel analogues). A nomogram was constructed to calculate the blood velocity in human RVs from the SBR values obtained in vivo. Blood velocities in RVs were determined in 12 normal eyes by using the laser speckle method and bidirectional LDV. Measurements were performed twice at the same site at 1-hour intervals. RESULTS: Measurements from a temporal superior artery (n = 12; mean ± SD) were blood velocity (V(mean)), 41.7 ± 4.2 mm/s; flow, 13.0 ± 3.2 µL/min; and diameter, 119.5 ±15.7 µm and time to complete one measurement, 65 ± 18 seconds, with the laser speckle apparatus; and V(mean), 37.7 ± 6.7 mm/s; flow, 11.7 ±3.0 µL/min; diameter, 111.1 ±16.6 µm; and measurement time, 112 ± 25 seconds, with the bidirectional LDV apparatus. The results obtained by the two methods correlated with each other (V(mean), r = 0.59, P = 0.023; flow, r = 0.83, P = 0.005; and diameter, r = 0.56, P = 0.032). The coefficients of reproducibility for V(mean), blood flow, and diameter measurement were 9.5% ± 2.5%, 10.5% ± 3.2%, and 5.3% ± 2.7% for the former and 15.3% ± 4.2%, 18.5% ± 4.1%, and 6.2% ± 2.2% for the latter, respectively. CONCLUSIONS: The laser speckle method accurately and reproducibly determines blood velocity in human RVs in less time than the LDV apparatus requires.

Endogenous Candida albicans infection causing subretinal abscess.

PURPOSE: We report a case of Candida albicans endophthalmitis with subretinal abscess formation in a patient who underwent liver transplantation. METHODS: Case report. RESULTS: A 51-year-old Japanese woman complained of deep pain and ciliary injection in her right eye. Three months prior, the patient had undergone liver transplantation for cirrhosis caused by hepatitis C. A slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and fundoscopy showed a yellowish-white subretinal mass lesion in the inferior peripheral fundus. Systemic and topical antibiotics did not prevent further progression of the infection. The patient underwent pars plana vitrectomy treatment three times and a histopathological study of a vitreous specimen revealed C. albicans to be the causative organism. CONCLUSION: A subretinal abscess, previously reported in Nocardia, Pseudomonas, Staphylococcus, and Aspergillus infection cases, can also occur in patients infected with Candida. Therefore, Candida infection should be considered as a potential cause of subretinal abscess in organ transplant recipients.

A placebo-controlled 3-year study of a calcium blocker on visual field and ocular circulation in glaucoma with low-normal pressure.

PURPOSE: To study the 3-year effect of oral nilvadipine, a calcium antagonist, on visual field performance and ocular circulation in open-angle glaucoma (OAG) with low-normal intraocular pressure (IOP). DESIGN: A randomized, placebo-controlled, double-masked, single-center trial. PARTICIPANTS: Patients with OAG who were younger than 65 years and had untreated IOP consistently of 16 mmHg or less. INTERVENTION: Oral nilvadipine (2 mg twice daily) or placebo was assigned randomly to patients fulfilling the criteria by the minimization method of balancing the groups according to age, refraction, and the mean deviation (MD) value (Humphrey Perimeter 30-2 SITA Standard Program; Humphrey Instruments, Inc., San Leandro, CA) of the eye with less negative MD. No topical ocular hypotensive drugs were prescribed. Visual field testing was performed every 3 months; fundus examination and IOP, blood pressure, and pulse rate measurements were carried out every month; and quantitative indexes of circulation in the optic disc rim (NB(ONH)) and choroid in the foveal area (NB(fovea)) were determined using the laser speckle method at 0, 3, 6, 12, 18, 24, 30, and 36 months. MAIN OUTCOME MEASURES: The time courses of MD, NB(ONH), and NB(fovea) in the eye with less negative MD. RESULTS: Thirty-three patients were enrolled; 17 were assigned to nilvadipine and 16 were assigned to placebo; 13 in each group completed the study. No significant intergroup difference was seen in age, refraction, or baseline values of any of the parameters. During the 3-year period, the IOP averaged 12.6 mmHg in the nilvadipine group and 12.8 mmHg in the placebo group (P>0.1), and no significant change from baseline or intergroup difference was seen in blood pressure or pulse rate. The estimated slope of change in the MD was less negative in the nilvadipine than in the placebo group (-0.01 vs. -0.27 decibels/year; P = 0.040). The NB(ONH) and NB(fovea) values remained increased compared with baseline for the study period by approximately 30% to 40% only in the nilvadipine group, and the intergroup difference was significant (P = 0.003 for NB(ONH) and P = 0.007 for NB(fovea)). CONCLUSIONS: Nilvadipine (2 mg twice daily) slightly slowed the visual field progression and maintained the optic disc rim, and the posterior choroidal circulation increased over 3 years in patients with OAG with low-normal IOP.

[Case of recurrent fungal endophthalmitis with suspected Munchausen syndrome].

PURPOSE: To report recurrent fungal endophthalmitis which developed after endogenous fungal endophthalmitis. The patient was suspected to be suffering from Munchausen syndrome. CASE: A 44-year-old woman contracted endogenous fungal endophthalmitis in her right eye in October 2000. After the endophthalmitis was healed by vitrectomy, corneal ulcer and endophthalmitis repeatedly occurred in the eye from an unknown cause. The patient finally lost the sight of her right eye. The corneal ulcer and endophthalmitis resulted from self-injury for which we found material evidence in the course of the treatment. Munchausen's syndrome was suspected but the patient persistently refused to see a psychiatrist. CONCLUSION: We must be prepared to provide mental and psychiatric care in addition to ophthalmological treatment for such a case.

Pharmacokinetic and pharmacodynamic analysis of systemic effect of topically applied timolol maleate ophthalmic gelling vehicle (Rysmon TG).

PURPOSE: The objective of this study was to evaluate the degree of systemic absorption and the systemic side effect after instillation of timolol maleate ophthalmic gelling vehicle in human. METHODS: A volunteer study was employed, and a randomized crossover design with the two phases was used. In one phase, the volunteers instilled a single drop of the 0.5% timolol maleate ophthalmic gelling vehicle; in the other phase, the volunteers instilled a single drop of the 0.5% timolol maleate ophthalmic solution. The plasma concentration of timolol and the heart rates were studied during the following 120 min and 60 min, respectively. RESULTS: The area under the blood concentration time curve (AUC) in timolol maleate ophthalmic gelling vehicle was lower than that in timolol maleate ophthalmic solution (p < 0.05). No differences were observed in heart rates between ophthalmic gelling vehicle and ophthalmic solution. The correlation between the calculated occupancy of beta-adrenergic receptors and the systemic side effects after instillation could be successfully analyzed with a pharmacokinetic and pharmacodynamic model, showing the predictability of the model for the systemic side effects of timolol. CONCLUSIONS: The result of our analysis clearly shows that timolol maleate ophthalmic gelling vehicle reduced the systemic absorption below that of ophthalmic solution, but the degree in difference of systemic effects was negligible.