Adverse reactions to ophthalmic medicines

To evaluate the incidence of and risk factors for persistently elevated intraocular pressure (IOP) and hypotony in patients who have undergone pars plana vitrectomy with silicone oil injection for the management of complex retinal detachment. The medical records of 532 patients who underwent silicone oil injection for the management of complex retinal detachments between January 1, 1991, and December 31, 1996, at the Bascom Palmer Eye Institute, Miami, Fla, were reviewed. Elevated IOP was defined as elevated IOP requiring an operation at any time postoperatively or a persistently elevated IOP of greater than 25 mm Hg at or after the 6-month visit. Hypotony was defined as a persistent IOP of 5 mm Hg or less at or after the 6-month visit. Patients with transient perioperative IOP fluctuations were not counted. Survival analysis for patients without cytomegalovirus retinitis (n = 383) revealed that 12.9% had an elevated IOP and 14.1% had hypotony by 6 months, 21% had an elevated IOP and 20.3% had hypotony by 1 year, and 29.5% had an elevated IOP and 27.3% had hypotony by 2 years. Among patients with cytomegalovirus retinitis (n = 149), none had a persistently elevated IOP, 10% had hypotony by 6 months, and 5.9% had persistently elevated IOP and 10% developed chronic hypotony by 1 year. A history of glaucoma before silicone oil retinal tamponade (P = .03), diabetes mellitus (P = .02), and a high IOP on the first postoperative day (P = .006) were risk factors for elevated postoperative IOP in patients without cytomegalovirus retinitis. Risk factors for postoperative hypotony in patients without cytomegalovirus retinitis included preoperative hypotony (P<.001) and aphakia (P = .03). An elevated or low IOP often develops postoperatively in patients without cytomegalovirus retinitis who undergo silicone oil injection for the management of complex retinal detachment. Risk factors for an elevated postoperative IOP include a history of glaucoma, diabetes mellitus, and a high IOP on the first postoperative day. Risk factors for hypotony include preoperative hypotony and aphakia.

The increase in intraocular pressure (IOP) associated with succinylcholine (Sch) has made its use in patients with open globe injuries controversial.Studies that have examined techniques to prevent the increase in IOP due to Sch have shown a larger increase in IOP from the stimulus of laryngoscopy and endotracheal intubation. The purpose of our study was to examine whether the combination of propofol and alfentanil would prevent the increase in IOP due to Sch as well as endotracheal intubation during a rapid sequence induction of anesthesia. Sixty patients were randomized to receive either thiopental 5 mg/kg and Sch 1.5 mg/kg (Group I), propofol 2 mg/kg and Sch 1.5 mg/kg (Group II), or propofol 2 mg/kg, alfentanil 40 micro gram/kg, and Sch 1.5 mg/kg (Group III). The IOP was measured continuously from baseline awake (control) values until 15 s after successful intubation. All three groups had a significant decrease in IOP with the induction of anesthesia. Succinylcholine produced a consistant increase in IOP from the postinduction low in Groups I and II, but this increase was not significantly higher than baseline. The postintubation IOPs in Groups I and II were significantly higher than baseline (P < 0.001). During the entire study period, the IOP in Group III never increased above baseline. The IOP in Groups I and II had already begun to decline by 15 s postintubation, suggesting that laryngoscopy and intubation have the greatest effect on increasing IOP. We conclude that the combination of propofol and alfentanil prevents the increase in IOP from Sch as well as the increase associated with endotracheal intubation during a rapid sequence induction of anesthesia. (Anesth Analg 1996;83:814-7)

ABSTRACTPurpose: To investigate changes in peripapillary retinal vessel density after acute intraocular pressure (IOP) elevation caused by laser peripheral iridotomy (LPI) in primary angle-closure suspects (PACS) by optical coherence tomography angiography (OCTA).Materials and Methods: Ninety-seven participants with PACS were included in this cross-sectional observational study. OCTA and IOP measurement were performed at baseline and 1 h after LPI. PACS eyes were further divided into three groups according to IOP increase 1 h after LPI (group 1 = IOP elevation <5 mmHg, 42eyes; group 2 = IOP elevation ≥5 mmHg and <10 mmHg, 34 eyes; group 3 = IOP elevation ≥10 mmHg, 21eyes). The changes of vessel density in radial peripapillary capillary (RPC) and entire retina were compared among groups.Results: When all eyes were included, the vessel density of RPC and entire retina 1 h after LPI were significantly decreased compared to the baseline (RPC: 64.5 ± 7.9 vs.67.8 ± 6.8, P < .001; retina: 86.3 ± 4.6 vs.88.3 ± 3.8, P < .001). There were significant differences among the three groups in the RPC and retinal vessel density at 1 h after LPI (RPC: 67.4 ± 7.3 vs. 63.2 ± 7.6 vs. 60.9 ± 7.5, P = .003; retinal: 87.7 ± 4.0 vs. 85.8 ± 4.5 vs. 84.3 ± 5.2, P = .015). In group 2 with an increased IOP from 5 mmHg to 10 mmHg, the reduction of vessel density in the RPC was more significant than that of the entire retina (RPC vs. retina: 7.1 ± 10.0% vs. 3.0 ± 4.4%, P = .006).Conclusions: LPI-induced IOP spikes resulted in a decrease in retina vessel density with PACS eyes by OCTA. The reduction of RPC vessel density was more significant than that of the entire retina in the subgroup of IOP increase from 5 to 10 mmHg. This suggests that vessel density in RPC was more sensitive to IOP increase than that of the entire retina in the peripapillary area.

IOP Changes after DSEK

Patients undergoing surgery in the prone position may be at risk for postoperative vision loss associated with increased intraocular pressure. The purpose of this systematic review and meta-analysis is to estimate the magnitude of the increase in intraocular pressure at specific perioperative time points in adult patients. The research question to be addressed is "What is the magnitude of the increase in intraocular pressure at specific perioperative time points in adults undergoing surgery in the prone position?" Comprehensive search strategies were used to identify nine eligible studies (N = 229). Standardized mean difference effect sizes were calculated for two intraoperative time points.Time points for meta-analysis were selected to achieve the greatest number of comparisons for analysis at each time point. Prediction intervals for each time point were also calculated to show the dispersion of true effect sizes around the mean. Meta-analysis showed that intraocular pressure increased significantly between induction of anesthesia and up to 10 minutes of prone position (T1: standardized mean difference [d] = 2.55; P < .001) and continued to increase significantly until the end of the prone position (T2: d = 3.44; P = .002). Intraocular pressure increases of this magnitude demonstrate the need for implementing interventions to reduce the risk for postoperative vision loss in patients undergoing surgery in the prone position. Implementing preoperative ophthalmologic examinations for patients undergoing surgery in the prone position may help to reduce the risk for ocular injury. Intraoperative interventions that can be implemented to reduce or mitigate the increase in intraocular pressure include implementing a 5- to 10-degree reverse Trendelenburg prone position, reducing the amount of time the patient is in the prone position, considering staged procedures, monitoring intraocular pressure, providing periodic position changes or rest periods, preventing pressure on the eye, and administering specific medications or anesthetics.

To investigate the time course of changes in optic nerve head (ONH) circulation after an acute increase in intraocular pressure (IOP), by using the laser speckle method, and to evaluate the effects of a calcium antagonist, the nitric oxide synthetase inhibitor, indomethacin, or sympathetic nerve amputation on the response in ONH circulation after an acute increase in IOP. In rabbits, the normalized blur (NB) level, a quantitative index of tissue blood velocity in the ONH, was monitored for 60 minutes after an increase in IOP from 20 mm Hg to 40, 50, or 60 mm Hg and for 25 seconds after increase in IOP from 20 mm Hg to 50 or 60 mm Hg with high time resolution. The effects of systemic administration of 1 micro g/kg per hour nilvadipine (a calcium antagonist), 30 mg/kg N(omega)-nitro-L-arginine (L-NAME), or 5 mg/kg indomethacin, or those of sympathetic nerve amputation on the time course of the changes in NB were studied. NB showed a quick recovery within several seconds after increase in IOP to 40 or 50 mm Hg, whereas no or little recovery occurred after an increase to 60 mm Hg. The nilvadipine treatment significantly increased NB at IOP of 20 mm Hg (baseline NB, P = 0.045) and apparently impaired the recovery of NB after the increase in IOP. After L-NAME administration, baseline NB significantly decreased (P = 0.028), and the NB recovery time was slightly but significantly prolonged (P = 0.012). Indomethacin showed no effects on baseline NB or NB recovery. Sympathetic nerve amputation increased baseline NB (P = 0.027), but did not influence NB recovery. The current results showed a quick recovery response in the ONH circulation after an acute increase in IOP in rabbits. A calcium antagonist impaired the response. Production of nitric oxide or prostaglandins or the sympathetic nervous system is probably not mainly responsible for the reaction.

BackgroundThe purpose of this study was to evaluate the safety and efficacy of a fixed combination of timolol maleate 0.5% + brimonidine tartrate 0.2% (Combigan®) for reduction for intraocular pressure (IOP) in patients with glaucoma when the dose frequency is increased from twice to three times daily.MethodsThe patients included had either primary open angle glaucoma or ocular hypertension. Those who were previously on treatment completed a drug washout period prior to inclusion. IOP was measured at baseline, after 4 weeks of treatment with Combigan twice daily, and again after a further 4 weeks of Combigan three times daily. Blood pressure, heart rate, and oxygen saturation were also recorded at each assessment.ResultsThirty-one eyes from 31 patients were included. Increasing the Combigan dose frequency resulted in a statistically significant (P < 0.001) additional reduction in IOP of 2.25 ± 1.18 mmHg, corresponding to a further 10.3% reduction in IOP from baseline. No local or systemic adverse effects were documented.ConclusionTreatment with Combigan three times daily was more effective in reducing IOP than the twice-daily regimen, with no increase in adverse effects.

To determine the extent to which (1) optic nerve tissue is displaced following mild acute elevation of intraocular pressure, and (2) clinically accessible measures at the anterior eye can be used as a surrogate for such displacements. We imaged the optic disc of 21 healthy subjects before and after intraocular pressure (IOP) elevation of ~10mmHg delivered by ophthalmodynamometry. Steady-state tissue displacement during IOP elevation was assessed axially from OCT data, and laterally from SLO data. Recovery from IOP elevation was assessed by tracking a single vertical B-scan through the cup centre. Anatomical structures were demarcated by three masked clinicians to determine lateral shifts for temporal cup edge and central disc vessels, and axial shifts of disc surface and anterior lamina cribrosa. Spatial maps of deformation were constructed within the demarcated cup and disc to assess within-tissue displacement. Measured displacements were correlated with corneal hysteresis, corneal thickness, and IOP. The temporal cup edge moved more temporally with higher baseline IOP (R2 =0.33, p=0.006) and with lesser elevation of IOP (R2 =0.43, p=0.001); it moved more superiorly for thinner corneas (R2 =0.35, p=0.007). Thinner corneas also produced less within-cup deformation, relative to that of the disc (R2 =0.39, p=0.004). Axial displacement of the lamina and lateral displacement of vessels were often substantial (lamina 20±15μm, range 1-60μm; vessels 37±25μm, range 2-102μm) but did not correlate with measured parameters. Recovery from IOP elevation did not take more than 300-400ms in any subject. Mild acute elevation of IOP produces large and rapidly reversible shifts in optic nerve tissue in young, healthy eyes. The resulting degree, direction and spatial distribution of cup movement are associated with IOP status and corneal thickness, but not corneal hysteresis.

Optic nerve dynein motor protein distribution changes with intraocular pressure elevation in a rat model of glaucoma

To evaluate the incidence and risk factors of intraocular pressure (IOP) elevation following triamcinolone acetonide (TA) administration. In this retrospective observational case series, patients (224 eyes of 202 patients) with diffuse diabetic macular edema (66 eyes), branch retinal vein occlusion (39 eyes), central retinal vein occlusion (25 eyes), exudative age-related macular degeneration (49 eyes), myopic choroidal neovascularization (10 eyes), uveitis (30 eyes), or other conditions (5 eyes) were administered an intravitreal or posterior sub-Tenon capsule injection, or both, of TA. Sub-Tenon capsule injection was performed on 106 eyes (STTA group). Intravitreal injection was performed on 118 eyes (IVTA group), of which 85 eyes underwent simultaneous intravitreal and sub-Tenon capsule injections. Mean follow-up after TA administration was 15.9 +/- 10.4 (range, 3-39) months. The sub-Tenon capsule injection and intravitreal injection of TA were compared with respect to the frequency of IOP elevation and the time between TA administration and the initial IOP elevation, and the possible risk factors responsible for IOP elevation were identified. There was no significant difference in frequency of IOP > 21 mmHg between the STTA group and the IVTA group (P = 0.0588). There was, however, a significant difference in the frequency of IOP > 30 mmHg between the two groups (P = 0.0004). In the IVTA group, more patients needed antiglaucoma medication than in the STTA group (P = 0.0052). The incidence rate of IOP elevation within 1 week after TA administration in the IVTA group was significantly higher than in the STTA group (P = 0.0154). Risk factors for IOP elevation included higher baseline IOP (P < 0.0001), younger patients (P = 0.0095), and simultaneous administration of sub-Tenon capsule and intravitreal injections (P = 0.0228). Careful follow-up of IOP is required after TA injections.

Intraocular Pressure Elevation within the First 24 Hours after Cataract Surgery in Patients with Glaucoma or Exfoliation Syndrome

Role of nitric oxide in optic nerve head blood flow regulation during an experimental increase in intraocular pressure in healthy humans

The acute biomechanical response of the optic nerve head (ONH) to intraocular pressure (IOP) elevations may serve as a biomarker for the development and progression of glaucoma. To evaluate the association between visual field loss and the biomechanical response of the ONH to acute transient IOP elevations. In this observational study, 91 Chinese patients (23 with primary open-angle glaucoma [POAG], 45 with primary angle-closure glaucoma, and 23 without glaucoma) were recruited from September 3, 2014, through February 2, 2017. Optical coherence tomography scans of the ONH were acquired at baseline and at 2 sequential IOP elevations (0.64 N and then 0.90 N, by applying forces to the anterior sclera using an ophthalmodynamometer). In each optical coherence tomography volume, lamina cribrosa depth (LCD) and minimum rim width (MRW) were calculated. The mean deviation (MD) and the visual field index (VFI), as assessed by automated perimetry, were correlated with IOP-induced changes of LCD and MRW globally and sectorially. The LCD, MRW, MD, and VFI. Among the 91 patients, 39 (42.9%) were women; the mean (SD) age was 65.48 (7.23) years. In POAG eyes, a greater change in LCD (anterior displacement) was associated with worse MD and VFI (R = -0.64; 95% CI, -0.97 to -0.31; P = .001; and R = -0.57; 95% CI, -0.94 to -0.19; P = .005, respectively) at the first IOP elevation, and a greater reduction in MRW was also associated with worse MD and VFI (first IOP elevation: R = -0.48; 95% CI, -0.86 to -0.09; P = .02; and R = -0.57; 95% CI, -0.94 to -0.20; P = .004, respectively; second IOP elevation: R = -0.56; 95% CI, -0.98 to -0.13; P = .01; and R = -0.60; 95% CI, -1.03 to -0.17; P = .008, respectively), after adjusting for age, sex, and baseline IOP. A correlation was found between the reduction in MRW in the inferior-temporal sector and the corresponding visual field cluster in POAG eyes at the second elevation (ρ = -0.55; 95% CI, -0.78 to -0.18; P = .006). The biomechanical response of the ONH to acute IOP elevations was associated with established visual field loss in POAG eyes, but not in primary angle-closure glaucoma eyes. This suggests that ONH biomechanics may be related to glaucoma severity in POAG and that the 2 glaucoma subgroups exhibit inherently different biomechanical properties.

Anterior chamber angle (ACA) narrowing continues to occur for at least 2 years after congenital cataract surgery. Risk factors for intraocular pressure (IOP) elevation after congenital cataract surgery were higher central corneal thickness (CCT) and surgery at <2 months. The purpose of this study was to study the changes in IOP and in the ACA during the first 2 years after pediatric cataract surgery and to determine risk factors for such changes. A retrospective observational study was done on infants who underwent pediatric cataract surgery in Cairo University Hospitals and completed a 1-year follow-up. Demographic and clinical characteristics were recorded including age at surgery, sex, corneal diameter, CCT pupil diameter, IOP, gonioscopic findings, presence of persistent hyperplastic primary vitreous, surgical approach, primary intraocular lens implantation, and perioperative subconjunctival steroid injection. Changes in IOP and in the ACA were recorded, and the risk factors for such changes were analyzed. Postoperative IOP elevation >18 mm Hg occurred in 23 eyes of 206 eyes (11%), who completed Year 1 and in 9 (13%) of 86 eyes who completed Year 2. Risk factors for IOP elevation were larger preoperative CCT (P=0.01) in Year 1, and younger age at surgery (P=0.01), and aphakia (P=0.05) in Year 2. In multivariate analysis only younger age at surgery was a risk factor for IOP elevation in Year 2. ACA narrowing occurred in 49% and in 21% of the examined eyes in Years 1 and 2, respectively. Aphakia was not a significant risk factor of angle narrowing in Years 1 and 2 (P=0.17 and 0.42, respectively). Higher preoperative CCT was a risk factor for early-onset IOP elevation. Surgery at >2 months was associated with lower susceptibility to late-onset IOP elevation.

Yoga is the most popular form of complementary therapy being practiced to maintain one’s physical and mental wellbeing. While yoga traditionally comprises advice for ethical lifestyle and spiritual practice, it is most often associated with physical postures (asanas), breathing techniques (pranayama), and meditation (dhyana). While these exercises are routinely safe, there are risks involved for certain patients including those suffering from or at risk of glaucoma. The effects of yoga on intraocular pressure (IOP) have been found to be bidirectional, and the exact mechanisms are not yet fully understood. The authors have reviewed literature to study the effect of yoga on IOP and glaucoma. They have observed a reduction of IOP in patients of glaucoma through Jyoti tratak (candle meditation) and slow yoga breathing exercises and a rapid increase in IOP immediately after head-down posture yoga.[1] Tratak kriya is said to lead to contraction and relaxation of ciliary muscles, which may possibly increase the aqueous humor outflow and subsequently decrease the IOP.[2] Dada et al.[3] have evaluated the effect of yoga and meditation on IOP, quality of life, stress markers, neurotrophins, and gene expression in patients with primary open-angle glaucoma and found an improvement in all parameters. On the other hand, progressive glaucomatous optic neuropathy and field loss in patients who regularly practiced Sirsasana (Headstand) has also been identified.[1,4,5] Four yogasanas [Adho Mukha Savasana (downward-facing dog), Uttanasana (standing forward bend), Halasana (plough pose), and Viparita Karani (legs-up-the-wall)] showed a 20–73.7% increase in IOP in all study subjects.[1] Yoga with head-down positions was associated with a rapid rise in IOP in glaucoma and healthy eyes and with the body vertical, with a doubling of the IOP, remaining elevated as long as the position was maintained.[1] Mani Baskaran et al.[6] observed a twofold increase in IOP during Sirsasana, which was maintained during the posture in all age groups irrespective of their ocular characteristics. Valsalva maneuver is known to affect IOP; so it is expected that breath-holding yogic exercises are likely to cause IOP elevation. Forced unilateral nostril breathing has also been observed to affect IOP significantly.[7] Rakstyte et al.[8] studied an impact on IOP before, during, and after Matsyasana (fish yoga pose) and found an increased IOP in head- down position which returns to the initial value shortly after. A case series by Mehrdad Malihi et al.[9] to study the effect of different body and head positions on IOP shows a lower measurement while sitting with a neutral neck position and a rise in IOP in all other positions. Acute angle-closure glaucoma attacks often precipitated by prone-position yoga exercises suggest that this position probably increases pupillary block in “at risk” eyes by causing the lens to fall onto the iris, which has been the principle of the prone provocative test for decades. Certain questions, however, remain unanswered. It is unclear whether yoga has any sustained effects on the IOP and optic nerve. Further research is needed to fully comprehend the mechanisms by which yoga exerts its effects and determine the types, optimal duration, and frequency of yoga practice for glaucoma patients. Future studies are also warranted to ascertain whether yoga-associated IOP changes are associated with parallel changes in perimetry and nerve fiber thickness and changes in cerebrospinal fluid pressure, blood pressure in lamina cribrosa capillaries, and the ocular blood flow. It is difficult to establish direct causality between different yogic postures and glaucomatous progression, but in patients with pre-existing glaucomatous optic neuropathy, dramatic changes in IOP can definitely be harmful. Inquiring about the practice of yoga in cases of unexplained progression despite an apparently well-controlled IOP can, therefore, be an important consideration. Relaxation and meditative aspects of yoga may help to reduce stress and improve the overall well-being of an individual which can be indirectly beneficial. The key is to “keep the head above the heart at all times.” It is also important to note that yoga should not replace traditional glaucoma treatment but rather be practiced/advised as a complementary therapy and glaucoma patients should consult their healthcare provider before beginning any new exercise or relaxation program, including yoga.