Journal Of Clinical & Experimental Ophthalmology[JOURNAL]
Sun
200 papers
Pupillographic investigation of the relative afferent pupillary defect associated with a midbrain lesion.
Kawasaki A, Miller NR, Kardon R
Ophthalmology · 2010 Jan · PMID 19923003 · Publisher ↗
OBJECTIVE: To identify clinical and pupillographic features of patients with a relative afferent pupillary defect (RAPD) without visual acuity or visual field loss caused by a lesion in the dorsal midbrain. DESIGN: Exper...
OBJECTIVE: To identify clinical and pupillographic features of patients with a relative afferent pupillary defect (RAPD) without visual acuity or visual field loss caused by a lesion in the dorsal midbrain. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Four patients with a dorsal midbrain lesion who had normal visual fields and a clinically detectable RAPD. METHODS: The pupil response from full-field and hemifield light stimulation over a range of light intensities was measured by computerized binocular pupillography. MAIN OUTCOME MEASURES: The mean of the direct and consensual pupil response to full-field and hemifield light stimulation was plotted as a function of stimulus light intensity. RESULTS: All 4 subjects showed decreased pupillographic responses at all intensities to full-field light stimulation in the eye with the clinical RAPD. The pupillographic responses to hemifield stimulation showed a homonymous pattern of deficit on the side ipsilateral to the RAPD, similar to that observed in a previously reported patient with an optic tract lesion. CONCLUSIONS: The basis of a midbrain RAPD is the nasal-temporal asymmetry of pupillomotor input that becomes manifest when a unilateral postchiasmal lesion interrupts homonymously paired fibers traveling in the contralateral optic tract or midbrain pathway to the pupillomotor center, respectively. The pupillographic characteristics of an RAPD resulting from a dorsal midbrain lesion thus resemble those of an RAPD resulting from a unilateral optic tract lesion, but without the homonymous visual field defect. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Orbital septum attachment on the levator aponeurosis in Asians: in vivo and cadaver study.
Kakizaki H, Leibovitch I, Selva D … +2 more , Asamoto K, Nakano T
Ophthalmology · 2009 Oct · PMID 19592104 · Publisher ↗
PURPOSE: To examine the anatomic relationships between the preaponeurotic fat pad, orbital septum, and the distal end of the anterior layer of the levator aponeurosis (DEALLA) in relation to the superior tarsal plate bor...
PURPOSE: To examine the anatomic relationships between the preaponeurotic fat pad, orbital septum, and the distal end of the anterior layer of the levator aponeurosis (DEALLA) in relation to the superior tarsal plate border. DESIGN: Prospective, clinical case series and experimental anatomic study. PARTICIPANTS: Twenty-two upper eyelids in 11 Asian patients (average age, 76.5 years) and 10 postmortem upper eyelid specimens of 7 Asians (average age, 81 years). METHODS: The relationships between the orbital septum, DEALLA, preaponeurotic fat pad, and the superior tarsal plate border were examined in vivo, during upper blepharoplasty. In cadavers, the orbital septum was exposed and excised from the DEALLA, and the distance from the superior tarsal plate border to the DEALLA was measured at 3 points: the center of the palpebral width, and 2 points located 7 mm medial and lateral to the center. MAIN OUTCOME MEASURES: The anatomic relationships of the orbital septum, DEALLA, and the preaponeurotic fat pad with the superior tarsal plate border. RESULTS: In vivo, the DEALLA was always located above the superior tarsal plate border, and the lower margin of the preaponeurotic fat was always positioned below the DEALLA and around the superior tarsal plate border. The lateral preaponeurotic fat in 4 eyelids showed extension beyond the superior tarsal border. In cadavers, the average distance from the superior tarsal plate border to the DEALLA was 3.7 mm centrally, 3.0 mm medially, and 0.9 mm laterally. In 3 specimens, the confluent part of the orbital septum and the levator aponeurosis reached the tarsus in the lateral area. CONCLUSIONS: Orbital septum attachment on the levator aponeurosis in Asians seems to be situated above the superior tarsal plate border in vivo, but the preaponeurotic fat extends beyond the DEALLA, sometimes reaching the tarsal plate. In some cadavers, the confluent part was found to be situated on the tarsus laterally.
Increased angiotensin II type 1 receptor expression in temporal arteries from patients with giant cell arteritis.
Dimitrijevic I, Malmsjö M, Andersson C … +2 more , Rissler P, Edvinsson L
Ophthalmology · 2009 May · PMID 19410957 · Publisher ↗
PURPOSE: Currently, giant cell arteritis (GCA) is primarily treated with corticosteroids or immunomodulating agents, but there is interest in identifying other noncorticosteroid alternatives. Similarities exist in the in...
PURPOSE: Currently, giant cell arteritis (GCA) is primarily treated with corticosteroids or immunomodulating agents, but there is interest in identifying other noncorticosteroid alternatives. Similarities exist in the injury pathways between GCA and atherosclerosis. Angiotensin II is a vasoactive peptide involved in vessel inflammation during atherosclerosis, and angiotensin II receptor inhibitors are effective in preventing atherosclerosis. The present study was performed to elucidate the role of angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors in GCA. DESIGN: Experimental retrospective immunohistochemical study of temporal arteries using archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: Ten patients with GCA and 10 control patients, who were clinically suspected of having GCA but were diagnosed as not having GCA, were included. METHODS: Immunohistochemistry, using anti-AT(1) and anti-AT(2) antibodies, was performed on formalin-fixed and paraffin-embedded temporal arteries. MAIN OUTCOME MEASURES: AT(1) and AT(2) receptor immunostaining intensity was quantified. RESULTS: Hematoxylin-eosin-stained sections of temporal arteries from patients with GCA showed intimal hyperplasia, internal elastic lamina degeneration, and band-shaped infiltrates of inflammatory cells, including lymphocytes, histocytes, and multinucleated giant cells. AT(1) receptor staining was primarily observed in the medial layer of the temporal arteries and was higher in the patients with GCA than in the control patients. This was a result of increased AT(1) receptor immunostaining of both vascular smooth muscle cells and infiltrating inflammatory cells. Only faint immunostaining was seen for AT(2) receptors, primarily in the endothelial cells, and to a lesser extent on the smooth muscle cells. Immunostaining with antibodies for the AT(2) receptor was similar in the patients with GCA and in controls. CONCLUSIONS: These results suggest that AT(1) receptors play a role in the development of GCA. Inhibition of the angiotensin system may thus provide a noncorticosteroid alternative for the treatment of GCA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Cellular and molecular origin of circumpapillary dysgenesis of the pigment epithelium.
Tosi J, Janisch KM, Wang NK … +4 more , Kasanuki JM, Flynn JT, Lin CS, Tsang SH
Ophthalmology · 2009 May · PMID 19410955 · Full text
PURPOSE: We studied clinical phenotyping and TEAD1 expression in mice and humans to gain a better understanding of the primary origin in the pathogenesis of circumpapillary dysgenesis of the pigment epithelium. DESIGN: O...
PURPOSE: We studied clinical phenotyping and TEAD1 expression in mice and humans to gain a better understanding of the primary origin in the pathogenesis of circumpapillary dysgenesis of the pigment epithelium. DESIGN: Observational case series and experimental study. PARTICIPANTS: Three female patients from an affected family were included for phenotypic study. Mice and human tissues were used for biochemistry and immunohistochemistry studies. METHODS: We performed genetic analyses and longitudinal clinical, imaging, and electrophysiologic studies in a 3-generation family. Western blotting and immunohistochemistry were used to detect TEAD1 expression in mice and human retinal tissues. MAIN OUTCOME MEASURES: Autofluorescence and optical coherence tomography (OCT) imaging were compared and reviewed from 3 patients. TEAD1 expression was compared in different tissues from mice and human samples. RESULTS: A point mutation at T1261 in TEAD1 was detected in the mother. Autofluorescence and OCT imaging studies revealed choroid is involved earlier than retinal pigment epithelium (RPE). From immunoblot analysis, we discovered that TEAD1 and its cofactors YAP65 and FOXA2 are expressed in the choroid. Immunohistochemical analysis on frozen sections of mouse retina supports immunoblot results. CONCLUSIONS: The primary cellular origin of circumpapillary dysgenesis of the pigment epithelium is within the choroid instead of the pigment epithelium. The loss of the RPE and photoreceptors in later stages of the disease is a secondary consequence of choroidal degeneration. Studies of the downstream targets of TEAD1 in choroidal cells will provide promising new research opportunities for the development of treatments for choroidal diseases. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Dynamic evaluation of sutureless vitrectomy wounds: an optical coherence tomography and histopathology study.
Taban M, Ventura AA, Sharma S … +1 more , Kaiser PK
Ophthalmology · 2008 Dec · PMID 19041476 · Publisher ↗
PURPOSE: To investigate the in vitro dynamic wound morphology of fresh 25- and 23-gauge sutureless sclerotomy wounds. DESIGN: Experimental study; laboratory investigation. PARTICIPANTS: Sixteen eyes of New Zealand white...
PURPOSE: To investigate the in vitro dynamic wound morphology of fresh 25- and 23-gauge sutureless sclerotomy wounds. DESIGN: Experimental study; laboratory investigation. PARTICIPANTS: Sixteen eyes of New Zealand white rabbits. METHODS: Eight cadaver heads were obtained, and the eyes were enucleated with their conjunctiva intact to simulate an intact globe. Four eyes were analyzed using 4 different wound types and cannula sizes: 25-gauge straight incision (group a); 25-gauge angled incision (group b); 23-gauge straight incision (group c); and 23-gauge angled incision (group d). Three incisions were created in each eye using either a 25- or 23-gauge trocar/cannula system. Intraocular pressure (IOP) was controlled with intraocular balanced salt solution infused through the infusion cannula. The incisions were imaged with a prototype, anterior segment spectral domain optical coherence tomography device under variable IOP to simulate successive blinks or rubbing of the eye and to evaluate the wounds in a dynamic state. Finally, India ink was applied to the surface of the eye under variable IOP to evaluate for wound leakage and potential ink ingress. The eyes were then analyzed by frozen section. MAIN OUTCOME MEASURES: Wound gaping as evaluated with optical coherence tomography (OCT) and presence of India ink particles in incisions evaluated by histology. RESULTS: Gross examination revealed obvious leakage of intraocular fluid in groups A and C (straight incisions) under variable IOP, with some even developing conjunctival blebs. Groups B and D (angled incisions) demonstrated minimal to no clinical leakage. Spectral domain optical coherence tomography demonstrated open wounds in straight incisions under all IOP conditions, with a slightly larger open wound under high IOP. Angled incisions demonstrated less wound gap overall and better wound apposition under high IOP versus low IOP. Histologic examination revealed India ink particles in all straight incisions with penetration across the whole incision in some wounds, whereas no ink particles were observed in angled incisions. CONCLUSIONS: Angled incisions have been proposed for sutureless vitrectomy to prevent wound leakage, hypotony, and the secondary risk of endophthalmitis. This study demonstrates that angled incisions provide better wound apposition under dynamic IOP conditions immediately after formation that simulate real-world situations: blinking, squeezing, or even rubbing of the eye. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
A corneal dystrophy associated with transforming growth factor beta-induced Gly623Asp mutation an amyloidogenic phenotype.
Auw-Haedrich C, Agostini H, Clausen I … +4 more , Reinhard T, Eberwein P, Schorderet DF, Gruenauer-Kloevekorn C
Ophthalmology · 2009 Jan · PMID 19019446 · Publisher ↗
PURPOSE: To present the light and electron microscopic findings of a unique corneal dystrophy never before described in a German family carrying the Gly623Asp Mutation of the TGFBI gene with late clinical onset. DESIGN:...
PURPOSE: To present the light and electron microscopic findings of a unique corneal dystrophy never before described in a German family carrying the Gly623Asp Mutation of the TGFBI gene with late clinical onset. DESIGN: Experimental study. PARTICIPANTS: Four affected and 6 nonaffected family members. METHODS: Slit-lamp examination, photographic documentation, and isolation of genomic DNA from peripheral blood leucocytes obtained from each family member examined. Exons 3, 4, 5, and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members. Five corneal buttons of 3 affected siblings were excised at the time of penetrating keratoplasty. Light and electron microscopic examination were performed including immunohistochemistry with antibodies against keratoepithelin (KE) 2 and 15. MAIN OUTCOME MEASURES: Clinical and histologic characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene. RESULTS: The specimens showed destructive changes in Bowman's layer and the adjacent stroma. Patchy Congo red-positive amyloid deposits were found within the epithelium in 1 cornea, in Bowman's layer and in the anterior stroma of all specimens also showing KE2, but not KE15, immunostaining. Electron microscopy revealed deposits mainly located in the anterior stroma and Bowman's layer and in small amounts in the basal area of some epithelial cells. The destroyed areas were strongly Alcian blue-positive, the Masson Trichrome stain proved mainly negative for the deposits. All affected but none of the unaffected family members had a heterozygous missense mutation in exon 14 of the TGFBI gene (G-->A transition at nucleotide 1915) replacing glycin by aspartic acid amino acid (Gly623Asp) at position 623 of the KE protein. CONCLUSIONS: In contrast with the patient carrying the Gly623Asp mutation of the TGFBI gene described by Afshari et al, our cases presented with Salzmann's nodular degeneration-like clinical features and their specimens contained KE2-positive amyloid. The reason for this now "meeting the expectation histologic phenotype" is unclear. The histologic findings emphasize that this is a unique corneal dystrophy, which shares no clinical characteristics with Reis-Bücklers' dystrophy and should be treated as a distinct entity. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
Assessment of stereoscopic optic disc images using an autostereoscopic screen - experimental study.
Habib MS, Lowell JA, Holliman NS … +4 more , Hunter A, Vaideanu D, Hildreth A, Steel DH
BMC Ophthalmol · 2008 Jul · PMID 18651983 · Full text
BACKGROUND: Stereoscopic assessment of the optic disc morphology is an important part of the care of patients with glaucoma. The aim of this study was to assess stereoviewing of stereoscopic optic disc images using an ex...
BACKGROUND: Stereoscopic assessment of the optic disc morphology is an important part of the care of patients with glaucoma. The aim of this study was to assess stereoviewing of stereoscopic optic disc images using an example of the new technology of autostereoscopic screens compared to the liquid shutter goggles. METHODS: Independent assessment of glaucomatous disc characteristics and measurement of optic disc and cup parameters whilst using either an autostereoscopic screen or liquid crystal shutter goggles synchronized with a view switching display. The main outcome measures were inter-modality agreements between the two used modalities as evaluated by the weighted kappa test and Bland Altman plots. RESULTS: Inter-modality agreement for measuring optic disc parameters was good [Average kappa coefficient for vertical Cup/Disc ratio was 0.78 (95% CI 0.62-0.91) and 0.81 (95% CI 0.6-0.92) for observer 1 and 2 respectively]. Agreement between modalities for assessing optic disc characteristics for glaucoma on a five-point scale was very good with a kappa value of 0.97. CONCLUSION: This study compared two different methods of stereo viewing. The results of assessment of the different optic disc and cup parameters were comparable using an example of the newly developing autostereoscopic display technologies as compared to the shutter goggles system used. The Inter-modality agreement was high. This new technology carries potential clinical usability benefits in different areas of ophthalmic practice.
Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study.
Lim KS, Nau CB, O'Byrne MM … +4 more , Hodge DO, Toris CB, McLaren JW, Johnson DH
Ophthalmology · 2008 May · PMID 18452763 · Full text
PURPOSE: To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility. DESIGN: Experimental s...
PURPOSE: To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility. DESIGN: Experimental study (double-masked, placebo-controlled, randomized paired comparison, 4-period crossover). PARTICIPANTS: Thirty healthy adult subjects. METHODS: Bimatoprost, latanoprost, travoprost, or a placebo was administered to the left eye once a day in the evening for 7 days, after a minimum 4-week washout period between each session. Tonographic outflow facility was measured by Schiøtz tonography and pneumatonography on day 7. On day 8, the aqueous humor flow rate and fluorophotometric outflow facility were measured by fluorophotometry. Uveoscleral outflow was calculated from the aqueous humor flow rate and outflow facility using the Goldmann equation. MAIN OUTCOME MEASURES: Facility of outflow, aqueous humor flow rate, intraocular pressure (IOP), and calculation of uveoscleral outflow. RESULTS: All medications lowered IOP relative to a placebo. None of the drugs affected aqueous humor production. All medications increased outflow facility compared with placebo when measured by Schiøtz and 2-minute pneumatonography (P< or =0.02); the apparent increase of outflow facility measured with fluorophotometry and 4-minute pneumatonography did not reach statistical significance. In contrast, uveoscleral outflow was significantly increased by all medications when calculated from 4-minute pneumatonography data, and fluorophotometry and Schiøtz data at higher episcleral venous pressures. The apparent increase found with 2-minute pneumatonography did not reach statistical significance. These differing results in the same patients indicate that differences in measurement techniques, and not differences in mechanism of action, explain previous conflicting published reports on the mechanism of action of the prostaglandins. CONCLUSIONS: Bimatoprost, latanoprost, and travoprost have similar mechanisms of action. All 3 drugs reduce IOP without significantly affecting the aqueous production rate. All drugs increase aqueous humor outflow, either by enhancing the pressure-sensitive (presumed trabecular) outflow pathway or by increasing the pressure-insensitive (uveoscleral) outflow, but the assessment of the amount of flow through each pathway depends upon the measurement technique.
Intraocular concentration of triamcinolone acetonide after intravitreal injection in the rabbit eye.
Kamppeter BA, Cej A, Jonas JB
Ophthalmology · 2008 Aug · PMID 18355920 · Publisher ↗
PURPOSE: To examine the decrease in the intraocular concentration of intravitreally injected triamcinolone acetonide over an 8-month period in a rabbit model. DESIGN: Experimental study. PARTICIPANTS: The study included...
PURPOSE: To examine the decrease in the intraocular concentration of intravitreally injected triamcinolone acetonide over an 8-month period in a rabbit model. DESIGN: Experimental study. PARTICIPANTS: The study included 18 white New Zealand rabbits. METHODS: The animals received an intravitreal injection of 6 mg triamcinolone acetonide. Vitreous and aqueous humor samples of the anterior and posterior chamber were taken at the first and third day, at 1 and 2 weeks, and at 1, 1.5, 2, 3, 6, and 8 months. The concentrations of triamcinolone were analyzed using a high-phase liquid chromatography assay. MAIN OUTCOME MEASURES: Intraocular concentration of triamcinolone during follow-up. RESULTS: Over the entire study period, triamcinolone concentrations were significantly higher in the vitreous samples than in the anterior chamber samples (day 1, 14 434+/-10 768 microg/l vs. 21.0+/-18.9 microg/l; day 30, 571.3+/-329.6 microg/l vs. 6.1+/-1.6 microg/l; month 8, 70.7+/-37.0 microg/l vs. 3.3+/-1.6 microg/l). In the anterior chamber, the triamcinolone concentrations were highest at 3 days after the injection (28.9+/-24.5 microg/l), and in the vitreous, the concentrations were highest at the first day (14,434.0+/-10,768 microg/l). Triamcinolone levels in the vitreous and in the anterior chamber followed a 2-compartment model, with an exponential decrease in the concentration within the first 4 weeks, followed by a steady decline over the following months. At 8 months, the triamcinolone concentrations were 70.7+/-37.0 microg/l in the vitreous samples and 3.3+/-1.6 microg/l in the anterior chamber samples. CONCLUSIONS: The decrease in the concentration of triamcinolone after an intravitreal injection of 6 mg in rabbits follows a 2-compartment model, with an exponential decrease in the first 4 weeks followed by a more linear decrease. During the entire study period, the triamcinolone concentration was significantly higher in the vitreous than in the anterior chamber. After a single intravitreal triamcinolone injection of 6 mg in rabbits, triamcinolone is detectable for at least 8 months after the injection.
Nonuniform pressure generation in the optic chiasm may explain bitemporal hemianopsia.
Kosmorsky GS, Dupps WJ, Drake RL
Ophthalmology · 2008 Mar · PMID 18082887 · Publisher ↗
PURPOSE: To measure the pressure in the temporal and central aspects of the chiasm simultaneously during compression of the optic chiasm from below with an expanding simulated tumor. DESIGN: Experimental study. METHODS:...
PURPOSE: To measure the pressure in the temporal and central aspects of the chiasm simultaneously during compression of the optic chiasm from below with an expanding simulated tumor. DESIGN: Experimental study. METHODS: Craniotomies were performed on 5 unfixed cadaveric specimens ranging in age from 49 to 89 years, and the optic chiasm was exposed. After a pediatric gauge Foley catheter was inserted into the sellar region, the temporal side of the chiasm (temporal aspect uncrossed fibers) was impaled with a 30-gauge needle connected to a pressure transducer. In like fashion, the central portion of the chiasm (crossed fibers) was impaled with another 30-gauge needle connected to a pressure transducer on a separate channel. The Foley catheter was inflated for a period of 30 seconds to 1 minute and the pressure in each channel continuously monitored. Multiple trials were performed on each of the 5 specimens. MAIN OUTCOME MEASURE: Pressure change between the temporal and nasal aspects of the optic chiasm. RESULTS: In all cases in which intrachiasmal pressure could be measured, higher pressures were always generated in the central aspect of the chiasm than in the temporal aspect of the chiasm. In cadaver 1, the mean central pressure was 19.75 mmHg, whereas the mean temporal pressure was 6 mmHg. In cadaver 5, the mean central pressure was 4 mmHg, whereas the mean temporal pressure was zero. Donors 70 and older demonstrated abnormally thin and frail chiasms that were unable to support a sustained pressure increase during simulated tumor expansion. CONCLUSIONS: During deformation of the optic chiasm from below by a radially expanding mass analogous to a pituitary tumor, the central aspect of the optic chiasm consistently manifests a higher pressure than the temporal aspect. It is hypothesized that the peculiar geometry of the optic chiasm renders the crossing nasal fibers more prone to a deformation stress exerted from below. Nonuniform pressure generation between the central and temporal aspects of the chiasm results in a greater effective stress on the crossing fibers of the chiasm and may be responsible for the clinical phenomenon of bitemporal hemianopsia.
Pharmacokinetics of intravitreal ranibizumab (Lucentis).
Bakri SJ, Snyder MR, Reid JM … +3 more , Pulido JS, Ezzat MK, Singh RJ
Ophthalmology · 2007 Dec · PMID 18054637 · Publisher ↗
PURPOSE: To describe the pharmacokinetics of 0.5 mg of intravitreal ranibizumab (Lucentis) and to compare it with that of 1.25 mg of intravitreal bevacizumab (Avastin), using the same rabbit model. DESIGN: Experimental a...
PURPOSE: To describe the pharmacokinetics of 0.5 mg of intravitreal ranibizumab (Lucentis) and to compare it with that of 1.25 mg of intravitreal bevacizumab (Avastin), using the same rabbit model. DESIGN: Experimental animal study. PARTICIPANTS: Twenty-eight Dutch-belted rabbits. METHODS: One eye of each of 20 rabbits was injected with 0.5 mg of intravitreal ranibizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Ranibizumab concentrations were measured in aqueous fluid, whole vitreous, and serum. A further 8 rabbits were used to measure serum and fellow ranibizumab at additional time points of 3 and 8 hours. MAIN OUTCOME MEASURES: Ranibizumab concentrations in the aqueous, vitreous, and serum. RESULTS: Although vitreous concentrations of ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days, concentrations of >0.1 microg/ml ranibizumab were maintained in the vitreous humor for 29 days. Ranibizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 17.9 microg/ml, 3 days after drug administration. Elimination of ranibizumab from the aqueous humor paralleled that found in the vitreous humor, with a half-life value of 2.84 days. No ranibizumab was detected in the serum or the fellow eye. CONCLUSION: In the rabbit, the vitreous half-life of 0.5-mg intravitreal ranibizumab is 2.88 days, shorter than the half-life of 1.25-mg intravitreal bevacizumab of 4.32 days. No ranibizumab was detected in the serum or the fellow uninjected eye; whereas small amounts of intravitreal bevacizumab have been detected in the serum and fellow uninjected eye.
Reproducibility of pattern electroretinogram in glaucoma patients with a range of severity of disease with the new glaucoma paradigm.
Fredette MJ, Anderson DR, Porciatti V … +1 more , Feuer W
Ophthalmology · 2008 Jun · PMID 17976726 · Full text
PURPOSE: To determine the reproducibility of the pattern electroretinogram with the new Pattern Electroretinogram for Glaucoma (PERGLA) recording paradigm in glaucoma patients with a range of severity. DESIGN: Experiment...
PURPOSE: To determine the reproducibility of the pattern electroretinogram with the new Pattern Electroretinogram for Glaucoma (PERGLA) recording paradigm in glaucoma patients with a range of severity. DESIGN: Experimental study. PARTICIPANTS: Fifty-three glaucoma patients were recruited for the study (mean age +/- standard deviation [SD], 69+/-11 years). Their mean deviation (MD) global indices on static automatic perimetry ranged from 2.16 to -31.36 decibels (mean MD, -9.05). INTERVENTION: All patients had pattern electroretinogram recordings done 5 times by the same operator, on 5 different days with the standardized PERGLA paradigm. MAIN OUTCOME MEASURES: Pattern electroretinogram amplitude (microvolts), phase (pi radians), response variability (coefficient of variation [CV] = SD/mean x 100) of amplitude and phase of 2 partial averages that build up the pattern electroretinogram waveform, interocular asymmetry in amplitude and phase (in terms of the CV generated by the pattern electroretinogram software), signal-to-noise (S/N) ratio, SDs, CV, and intraclass correlation coefficient (ICC). All analyses were done on one eye of each subject, except when interocular asymmetry was studied. RESULTS: The CVs of intrasession variabilities in amplitude and phase were 12.08% and 2.20%, respectively, and those of intersession variabilities were 20.82% and 4.17%. The pattern electroretinogram produced intersession ICCs in amplitude and phase of 0.791 and 0.765, respectively. These ICCs were significantly higher than the ICCs for pattern electroretinogram interocular asymmetry in amplitude and phase (0.659 [P<0.05] and 0.571 [P<0.05], respectively). On average, the pattern electroretinogram S/N ratio in glaucomatous patients was about 5:1. CONCLUSIONS: The reproducibility of PERGLA in glaucomatous patients is sufficiently good for it to be considered a useful complementary clinical tool. Being more reproducible, direct measures of amplitude and phase should be more useful in monitoring progression than interocular asymmetry comparisons.
Reproducibility of peripapillary retinal nerve fiber thickness measurements with stratus OCT in glaucomatous eyes.
Budenz DL, Fredette MJ, Feuer WJ … +1 more , Anderson DR
Ophthalmology · 2008 Apr · PMID 17706287 · Publisher ↗
PURPOSE: To determine the reproducibility of Stratus OCT peripapillary retinal nerve fiber layer (RNFL) measurements in glaucomatous eyes. DESIGN: Experimental study. PARTICIPANTS: Fifty-one stable glaucoma patients with...
PURPOSE: To determine the reproducibility of Stratus OCT peripapillary retinal nerve fiber layer (RNFL) measurements in glaucomatous eyes. DESIGN: Experimental study. PARTICIPANTS: Fifty-one stable glaucoma patients with a range of severity. METHODS: Peripapillary RNFL thickness was measured using the Standard and Fast scan protocols of Stratus optical coherence tomography (OCT) 3 times on the same day to determine intrasession variability and on 5 different days within a 2-month period to determine intersession variability. The same instrument was used by the same operator for all scans. MAIN OUTCOME MEASURES: Intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability. RESULTS: For mean RNFL thickness, the intrasession and intersession ICCs for the Standard and Fast scans were 0.98 and 0.96, respectively. The COV ranged from 3.8% to 5.2%. Test-retest variability was approximately 7 microm between sessions, most of which can be attributed to the approximate 5-microm variability within each session. For quadrants, the ICC was 0.9 or higher and the COV was under 10% except nasally. Test-retest variability for quadrant measurements ranged from 6 to 16 microm. For clock hours, test-retest variability approached 20 microm between sessions in some sectors. In general, the ICC was lower in the nasal region than elsewhere. Variability was greater the smaller the area over which RNFL thickness was determined. Intrasession variability was not a predictor of intersession variability in individual subjects (P Standard = 0.72, P Fast = 0.28). There was no relationship between variability and mean RNFL thickness (P Standard = 0.28, P Fast = 0.93). CONCLUSIONS: The reproducibility of Stratus OCT for RNFL thickness is sufficiently good to be useful clinically as a measure of glaucoma progression. When comparing 2 mean RNFL values on different days in the same eye, an 8-microm decrease in thickness might be accepted as within normal limits of test-retest variability with 95% tolerance. For quadrants and clock-hour sectors, variability is higher, and more detailed calculations are necessary.
Graft central thickness measurement by rotating Scheimpflug camera and ultrasound pachymetry after penetrating keratoplasty.
de Sanctis U, Missolungi A, Mutani B … +1 more , Grignolo FM
Ophthalmology · 2007 Aug · PMID 17678690 · Publisher ↗
PURPOSE: To assess agreement between rotating Scheimpflug camera and ultrasound pachymetry in measuring graft central thickness, and compare reproducibility/repeatability of these methods in corneal grafts and normal cor...
PURPOSE: To assess agreement between rotating Scheimpflug camera and ultrasound pachymetry in measuring graft central thickness, and compare reproducibility/repeatability of these methods in corneal grafts and normal corneas. DESIGN: Experimental study. PARTICIPANTS: Sixty-five patients with corneal grafts after penetrating keratoplasty and 20 controls with normal corneas (1 eye per patient). METHODS: In 45 eyes with clear grafts after penetrating keratoplasty, graft central thickness measurements were compared between the 2 methods (examiner 1). In another 20 eyes with clear grafts after penetrating keratoplasty and in 20 normal corneas, 2 independent examiners (1 and 2) each employed both methods in a first session to assess interexaminer reproducibility; measurements were then repeated by examiner 1 alone in a second session, and differences with his first session measurements used to assess intraexaminer repeatability. Paired t test, intraclass correlation coefficient (ICC) and 95% limits of agreement (95% LoA) were calculated to assess differences, correlation, and variability of methods, examiners, and first-second measurements. MAIN OUTCOME MEASURES: Graft central thickness measurements by 2 methods. Difference of measurements by 2 examiners; and difference of first-second measurements by 1 examiner, in corneal grafts and normal corneas with both methods. RESULTS: Mean graft central thickness measurement was 556.9+/-41.8 microm with the rotating Scheimpflug camera and 561.8+/-40.8 with ultrasound pachymetry (P = 0.012). There was a significant linear correlation in graft central thickness measurement between the 2 methods (r = 0.93; P<0.001) and 95% LoAs were -34 to +23.4 microm. Interexaminer and intraexaminer correlations were high with both methods: ICCs were > or = 0.94 in corneal grafts and > or = 0.98 in normal corneas. Interexaminer and intraexaminer variability was slightly higher with the rotating Scheimpflug camera than with ultrasound pachymetry, and in corneal grafts than in normal corneas. CONCLUSIONS: Measurements of graft central thickness with the rotating Scheimpflug camera, although slightly lower, were comparable to those with ultrasound pachymetry. The reproducibility and repeatability of these methods in corneal grafts are only slightly lower than in normal corneas.
Assessment of eye bank-prepared posterior lamellar corneal tissue for endothelial keratoplasty.
Rose L, Briceño CA, Stark WJ … +2 more , Gloria DG, Jun AS
Ophthalmology · 2008 Feb · PMID 17599413 · Publisher ↗
OBJECTIVE: To evaluate eye bank-prepared tissue for Descemet's stripping automated endothelial keratoplasty (DSAEK). DESIGN: Experimental study and retrospective case series. PARTICIPANTS: Seventeen human donor corneas a...
OBJECTIVE: To evaluate eye bank-prepared tissue for Descemet's stripping automated endothelial keratoplasty (DSAEK). DESIGN: Experimental study and retrospective case series. PARTICIPANTS: Seventeen human donor corneas and 4 recipient patients undergoing DSAEK surgery. METHODS: Corneal-scleral discs were obtained. Specular microscopy and pachymetry were performed. A designated Tissue Banks International technician used a microkeratome to prepare a flap. Posterior bed thickness was measured. The sectioned tissue was stored, and at 24 and 48 hours, pachymetry was repeated. At 48 hours, specular microscopy was repeated, and endothelial cell viability was assessed with trypan blue. Descemet's stripping automated endothelial keratoplasty was performed in 4 patients using eye bank-prepared posterior lamellar tissue. MAIN OUTCOME MEASURES: Corneal tissue was assessed with the following parameters: corneal thickness measured with ultrasonic pachymetry, cell density counts measured with a keratoanalyzer, and cell viability as observed with trypan blue exclusion. Patient outcomes were measured by changes in visual acuity (VA) and the presence of a clear graft. RESULTS: Donor corneal pachymetry before sectioning averaged 599+/-52 microm. Immediately after sectioning with a microkeratome set at a depth of 300 microm, mean posterior bed thickness was 328+/-95 microm. Thus, the mean cutting depth achieved by the microkeratome when set at 300 micrometers averaged 271+/-83 microm. After storage for 24 hours, the posterior beds measured 352 microm, an average swelling of 24 (7%) microm (P = 0.14). After 48 hours, the posterior beds measured 382 microm, an average swelling of 54 (16%) microm (P = 0.02). Cell counts 48 hours after sectioning decreased by an average of 11% (P = 0.10). Endothelial cell staining confirmed improvement in postsectioning morphology and survival with increased technician experience. All 4 patients receiving eye bank-prepared DSAEK tissue showed uncomplicated postoperative results, with improvement in VA. CONCLUSIONS: The microkeratome cutting depth was moderately accurate. Pachymetry, cell density, and cell viability of sectioned tissue after 48 hours in storage were encouraging overall. Initial clinical results of eye bank-prepared DSAEK tissue showed uncomplicated postoperative courses and improved VA. Additional studies are needed to follow the long-term outcomes in the recipients of these tissues.
Biomechanical assessment of radial optic neurotomy.
Friberg TR, Smolinski P, Hill S … +1 more , Kurup SK
Ophthalmology · 2008 Jan · PMID 17544511 · Publisher ↗
PURPOSE: A biomechanical model was constructed to simulate the potential therapeutic effect that the surgical procedure radial optic neurotomy (RON) would have on an eye with a central retinal vein occlusion. DESIGN: Exp...
PURPOSE: A biomechanical model was constructed to simulate the potential therapeutic effect that the surgical procedure radial optic neurotomy (RON) would have on an eye with a central retinal vein occlusion. DESIGN: Experimental study. CONTROLS: Model eyes undergoing RON were compared to control eyes under the same baseline conditions. INTERVENTION: Radial optic neurotomy. We modeled the optic nerve, lamina cribrosa, and the sclera separately and then reassembled the components. Material properties of the sclera and lamina cribrosa were extracted from the literature and both stiff and more elastic values were used for the optic nerve. Intraocular and arterial pressures were varied across a wide range in the analysis. MAIN OUTCOME MEASURE: Change in central retinal vein lumen size. RESULTS: Over a clinically relevant range of boundary conditions, the increase in the lumen area of the central retinal vein lumen after RON remained trivial, ranging from 1% to a maximum of 5%. CONCLUSIONS: The biomechanical effect of RON is negligible, and is unlikely to be a procedure that could mechanically ameliorate the clinical sequelae of a central vein occlusion.
Pharmacokinetics of intravitreal bevacizumab (Avastin).
Bakri SJ, Snyder MR, Reid JM … +2 more , Pulido JS, Singh RJ
Ophthalmology · 2007 May · PMID 17467524 · Publisher ↗
PURPOSE: To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin). DESIGN: Experimental animal study. PARTICIPANTS: Twenty Dutch-belted rabbits. METHODS: One eye of each of 20 rabbits was injecte...
PURPOSE: To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin). DESIGN: Experimental animal study. PARTICIPANTS: Twenty Dutch-belted rabbits. METHODS: One eye of each of 20 rabbits was injected with 1.25 mg of intravitreal bevacizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in aqueous fluid, whole vitreous, and serum. MAIN OUTCOME MEASURES: Bevacizumab concentrations in the aqueous, vitreous, and serum. RESULTS: Whereas vitreous concentrations of bevacizumab declined in a monoexponential fashion with a half-life of 4.32 days, concentrations of >10 microg/ml bevacizumab were maintained in the vitreous humor for 30 days. Bevacizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 37.7 microg/ml 3 days after drug administration. A maximum serum concentration of 3.3 mug/ml was achieved 8 days after intravitreal injection and the concentration fell below 1 microg/ml 29 days after injection. Elimination of bevacizumab from the aqueous humor and serum paralleled that found in the vitreous humor, with half-life values of 4.88 days and 6.86 days, respectively. Very low concentrations of bevacizumab were detected in the fellow uninjected eye. Concentrations of bevacizumab in the vitreous of the fellow eye varied incrementally, from 0.35 ng/ml at 1 day to 11.17 ng/ml at 4 weeks. Concentrations of bevacizumab in the aqueous humor of the fellow eye reached their peak at 1 week, at 29.4 ng/ml, and declined to 4.56 ng/ml at 4 weeks. CONCLUSION: The vitreous half-life of 1.25 mg intravitreal bevacizumab is 4.32 days in a rabbit eye. Very small amounts of bevacizumab were detected in the serum and in the fellow uninjected eye.
Effects of subretinal injections of indocyanine green, trypan blue, and glucose in rabbit eyes.
Penha FM, Maia M, Eid Farah M … +5 more , Príncipe AH, Freymüller EH, Maia A, Magalhães O, Smith RL
Ophthalmology · 2007 May · PMID 17292475 · Publisher ↗
PURPOSE: To evaluate the effects of subretinal injections of indocyanine green (ICG), trypan blue, glucose (GL), and balanced salt solution (BSS) in rabbits. DESIGN: Experimental study. PARTICIPANTS: Twenty Dutch-belted...
PURPOSE: To evaluate the effects of subretinal injections of indocyanine green (ICG), trypan blue, glucose (GL), and balanced salt solution (BSS) in rabbits. DESIGN: Experimental study. PARTICIPANTS: Twenty Dutch-belted rabbits. METHODS: Ten animals underwent vitrectomy and subretinal injection of 0.02 ml of either 0.05% ICG (279 milliosmoles [mOsm]), 0.15% trypan blue (312 mOsm), 5% GL (280 mOsm), or BSS (300 mOsm), which was tested as a control. Ten additional animals underwent subretinal injection of 0.02 ml of 0.046% ICG (251 mOsm), 0.13% trypan blue (260 mOsm), 4.6% GL (253 mOsm), or BSS (300 mOsm). Animals were examined 6, 12, and 24 hours and 14 days after the procedure by fluorescein angiography and fundus evaluation; histologic studies were performed by light and transmission electron microscopy. MAIN OUTCOME MEASURES: Clinical outcome, fluorescein angiography, and histopathologic results. RESULTS: All subretinal blebs were flat 24 hours after the procedure. Fluorescein angiography showed window defects where ICG and trypan blue had been injected. Subretinal BSS and GL resulted in minimal abnormalities of the photoreceptor outer segments (POS) during follow-up. Hypo-osmolar GL caused edema in all retinal layers; pyknosis of the outer nuclear layer (ONL) was observed 24 hours after injection. Subretinal injection of trypan blue resulted in histologic abnormalities 24 hours and 14 days after surgery. Hypo-osmolar trypan blue caused edema of the POS and the photoreceptor inner segments and pyknosis of the ONL 6 and 12 hours after surgery; the retinal pigment epithelium also was affected 24 hours and 14 days after surgery. Subretinal injection of iso-osmolar and hypo-osmolar ICG caused severe damage of all retinal layers during the entire follow-up. CONCLUSIONS: Subretinal injection of 0.05% ICG results in more substantial retinal damage than that associated with the 0.15% trypan blue subretinal injection. The damage induced by hypo-osmolar solutions was more important than that caused by the iso-osmolar solutions. These findings emphasize that care must be taken regarding the solution osmolarity and that subretinal migration of these substances should be avoided during macular hole surgery.
Are disposable prisms an adequate alternative to standard Goldmann tonometry prisms in glaucoma patients?
Maino AP, Morgan LH, Hercules BL … +1 more , Tullo AB
Ophthalmology · 2006 Oct · PMID 17011960 · Publisher ↗
PURPOSE: To evaluate the accuracy and reliability of 2 single-use tonometry devices (Tonosafe and Tonojet) as an alternative to standard Goldmann prisms in patients attending dedicated glaucoma clinics. DESIGN: Prospecti...
PURPOSE: To evaluate the accuracy and reliability of 2 single-use tonometry devices (Tonosafe and Tonojet) as an alternative to standard Goldmann prisms in patients attending dedicated glaucoma clinics. DESIGN: Prospective experimental study with human subjects. PARTICIPANTS: Two hundred forty glaucoma patients who attended 2 glaucoma clinics at the Stepping Hill Hospital between January and February 2005. METHODS: During each examination, intraocular pressure (IOP) was measured 3 times, using the standard Goldmann prism, Tonosafe, and Tonojet, respectively. The prism sequence was predetermined at random using a computer, and the measurements were taken at 5-minute intervals. Data were analyzed using the Bland-Altman method of differences. MAIN OUTCOME MEASURE: Intraocular pressure. RESULTS: Intraocular pressure ranged from 6 to 68 mmHg. Linear regression analysis indicated that there was a proportional bias between Goldmann and Tonosafe (r2 = 0.368, P<.001), especially for values higher than 25 mmHg. On the other hand, there was no statistically significant proportional bias between Goldmann and Tonojet (r2 = 0.006, P = 0.14). CONCLUSIONS: Caution should be exercised when using Tonosafe prisms in the presence of IOP higher than 25 mmHg. On the other hand, Tonojet is an adequate and useful alternative to the Goldman tonometer for glaucoma patients.
Repeatability and reproducibility of posterior corneal curvature measurements by combined scanning-slit and placido-disc topography after LASIK.
Maldonado MJ, Nieto JC, Díez-Cuenca M … +1 more , Piñero DP
Ophthalmology · 2006 Nov · PMID 16935339 · Publisher ↗
OBJECTIVE: To assess the repeatability and reproducibility of posterior corneal curvature (PCC) measurements made by combined scanning-slit/Placido-disc topography (Orbscan II) after LASIK. DESIGN: Experimental instrumen...
OBJECTIVE: To assess the repeatability and reproducibility of posterior corneal curvature (PCC) measurements made by combined scanning-slit/Placido-disc topography (Orbscan II) after LASIK. DESIGN: Experimental instrument validation study. PARTICIPANTS: We recruited 22 consecutive postmyopic LASIK patients for the repeatability study and another 50 consecutive postmyopic LASIK patients for the reproducibility study. METHODS: To analyze intrasession repeatability, 1 examiner measured 22 postmyopic LASIK eyes 10 times successively in the shortest time possible. To study intersession reproducibility, the same operator obtained measurements from another 50 eyes with stable refraction in 2 consecutive visits at the same time of the day between 6 and 9 months after myopic LASIK. We explored any association between residual stromal bed thickness and measurement variability. MAIN OUTCOME MEASURES: Orbscan II scanning-slit PCC data, precision, within-subject coefficient of variation (CV(w)), limits of agreement (LoA), and intraclass correlation coefficient (ICC). RESULTS: For intrasession repeatability, precision was 0.067 mm (best-fit sphere [BFS]), 0.110 diopters (D; power within 5 mm), 0.158 D (power within 3 mm), and 0.46 (eccentricity). Repeatability was high for PCC BFS and power measurements within 3-mm and 5-mm zones (CV(w) ranged from 0.5%-1.2%) but poor for eccentricity data (CV(w), 31.6%). Correspondingly, ICCs ranged from 0.89 to 0.98 for PCC BFS and power, and the ICC was 0.20 for PCC eccentricity values. For intersession reproducibility, on average, no difference in PCC measurements could be found, indicating that when there is variability, it is due to random factors. The width of the 95% LoA between sessions was clinically acceptable for BFS (0.25 mm) and power (0.4 D [within 5 mm] and 0.6 D [within 3 mm]). Similarly, ICCs indicated good intersession reliability for BFS and power (0.98, 0.96, and 0.85 for BFS, power within 5 mm, and power within 3 mm, respectively) but poor reliability for eccentricity (0.59). Repeatability and reproducibility were unrelated to stromal bed thickness. CONCLUSIONS: Orbscan II provides reliable post-LASIK PCC data for symmetrical parameters (BFS and power), independent of the residual stromal bed thickness, but is unreliable for measurements that are radially asymmetrical (eccentricity). Orbscan II is useful for monitoring the PCC after LASIK once the early postoperative period is over.
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