The ontogeny of muscle structure and locomotory function in the long-finned squid Doryteuthis pealeii.

Understanding the extent to which changes in muscle form and function underlie ontogenetic changes in locomotory behaviors and performance is important in understanding the evolution of musculoskeletal systems and also the ecology of different life stages. We explored ontogenetic changes in the structure, myosin heavy chain (MHC) expression and contractile properties of the circular muscles that provide power for jet locomotion in the long-finned squid Doryteuthis pealeii. The circular muscle fibers of newly hatched paralarvae had different sizes, shapes, thick filament lengths, thin:thick filament ratio, myofilament organization and sarcoplasmic reticulum (SR) distribution than those of adults. Viewed in cross section, most circular muscle cells were roughly triangular or ovoid in shape with a core of mitochondria; however, numerous muscle cells with crescent or other unusual cross-sectional shapes and muscle cells with unequal distributions of mitochondria were present in the paralarvae. The frequency of these muscle cells relative to 'normal' circular muscle cells ranged from 1:6 to 1:10 among the 19 paralarvae we surveyed. The thick filaments of the two types of circular fibers, superficial mitochondria-rich (SMR) and central mitochondria-poor (CMP), differed slightly in length among paralarvae with thick filament lengths of 0.83+/-0.15 microm and 0.71+/-0.1 microm for the SMR and CMP fibers, respectively (P 0.05; ANOVA). During ontogeny the thick filament lengths of both the CMP and SMR fibers increased significantly to 1.78+/-0.27 microm and 3.12+/-0.56 microm, respectively, in adults (P<0.0001 for both comparisons; ANOVA with Tukey's highly significant difference post hoc tests). When sectioned parallel to their long axes, the SMR and CMP fibers of both paralarvae and adults exhibited the myofilament arrangements typical of obliquely striated muscle cells but the angle of obliquity of the dense bodies was 22.8+/-2.4 deg. and 4.6+/-0.87 deg. for paralarvae and adults, respectively. There were also differences in the distribution of the anastomosing network of SR. In paralarvae, the outer and central zones of SR were well developed but the intramyoplasmic zone was greatly reduced in some cells or was scattered non-uniformly across the myoplasm. Whereas in adults the intramyoplasmic SR region was composed primarily of flattened tubules, it was composed primarily of rounded vesicles or tubules when present in the paralarvae. The ontogenetic differences in circular muscle structure were correlated with significant differences in their contractile properties. In brief tetanus at 20 degrees C, the mean unloaded shortening velocity of the paralarval circular muscle preparations was 9.1 L(0) s(-1) (where L(0) was the preparation length that generated the peak isometric stress), nearly twice that measured in other studies for the CMP fibers of adults. The mean peak isometric stress was 119+/-15 mN mm(-2) physiological cross section, nearly half that measured for the CMP fibers of adults. Reverse transcriptase-polymerase chain reaction analysis of paralarval and adult mantle samples revealed very similar expression patterns of the two known isoforms of squid MHC. The ontogenetic differences in the structure and physiology of the circular muscles may result in more rapid mantle movements during locomotion. This prediction is consistent with jet pulse durations observed in other studies, with shorter jet pulses providing hydrodynamic advantages for paralarvae.

Mystery of the toxic flea dip: an interactive approach to teaching aerobic cellular respiration.

We designed an interrupted case study to teach aerobic cellular respiration to major and nonmajor biology students. The case is based loosely on a real-life incident of rotenone poisoning. It places students in the role of a coroner who must determine the cause of death of the victim. The case is presented to the students in four parts. Each part is followed by discussion questions that the students answer in small groups prior to a classwide discussion. Successive parts of the case provide additional clues to the mystery and help the students focus on the physiological processes involved in aerobic respiration. Students learn the information required to solve the mystery by reading the course textbook prior to class, listening to short lectures interspersed throughout the case, and discussing the case in small groups. The case ends with small group discussions in which the students are given the names and specific molecular targets of other poisons of aerobic respiration and asked to determine which process (i.e., glycolysis, citric acid cycle, or the electron transport chain) the toxin disrupts.

Ontogenetic changes in fibrous connective tissue organization in the oval squid, Sepioteuthis lessoniana Lesson, 1830.

Ontogenetic changes in the organization and volume fraction of collagenous connective tissues were examined in the mantle of Sepioteuthis lessoniana, the oval squid. Outer tunic fiber angle (the angle of a tunic collagen fiber relative to the long axis of the squid) decreased from 33.5 degrees in newly hatched animals to 17.7 degrees in the largest animals studied. The arrangement of intramuscular collagen fiber systems 1 (IM-1) and 2 (IM-2) also changed significantly during ontogeny. Because of the oblique trajectory of the IM-1 collagen fibers, two fiber angles were needed to describe their organization: (1) IM-1(SAG), the angle of an IM-1 collagen fiber relative to the squid's long axis when viewed from a sagittal plane and (2) IM-1(TAN), the angle of an IM-1 collagen fiber relative to the squid's long axis when viewed from a plane tangential to the outer curvature of the mantle. The sagittal component (IM-1(SAG)) of the IM-1 collagen fiber angle was lowest in hatchling squid (32.7 degrees ) and increased exponentially during growth to 43 degrees in squid with a dorsal mantle length (DML) of 15 mm. In squid larger than 15 mm DML, IM-1(SAG) fiber angle did not change. The tangential component (IM-1(TAN)) of IM-1 collagen fiber angle was highest in hatchling squid (39 degrees ) and decreased to 32 degrees in the largest squid examined. IM-2 collagen fiber angle (the angle of an IM-2 collagen fiber relative to the outer surface of the mantle) was lowest in hatchling squid (34.6 degrees ) and increased exponentially to about 50 degrees in 15-mm DML animals. In squid larger than 15 mm DML, IM-2 fiber angle increased slightly with size. The volume fraction of collagen in IM-1 and IM-2 increased 68 and 36 times, respectively, during growth. The ontogenetic changes in the organization of collagen fibers in the outer tunic, IM-1, and IM-2 may lead to ontogenetic differences in the kinematics of mantle movement and in elastic energy storage during jet locomotion.

Ontogenetic changes in mantle kinematics during escape-jet locomotion in the oval squid, Sepioteuthis lessoniana Lesson, 1830.

We investigated the kinematics of mantle movement during escape jet behavior in an ontogenetic series of Sepioteuthis lessoniana, the oval squid. Changes in mantle diameter during the jet were measured from digitized S-VHS video fields of tethered animals that ranged in age from hatchlings to 9 weeks. The amplitude of both mantle contraction and mantle hyperinflation (expressed as percent change from the resting mantle diameter) during an escape jet was significantly greater in hatchlings than in older, larger squid (P < 0.05). The maximum amplitude of mantle contraction during the escape jet decreased from an average of -40% in hatchlings to -30% in the largest animals studied. The maximum amplitude of mantle hyperinflation decreased from an average of 18% in hatchlings to 9% in the largest squid examined. In addition, the maximum rate of mantle contraction decreased significantly during ontogeny (P < 0.05), from a maximum of 8.6 mantle circumference lengths per second (L/s) in hatchlings to 3.8 L/s in the largest animals studied. The ontogenetic changes in the mantle kinematics of the escape jet occurred concomitantly with changes in the organization of collagenous connective tissue fiber networks in the mantle. The alteration in mantle kinematics during growth may result in proportionately greater mass flux during the escape jet in newly hatched squid than in larger animals.

myo-Inositol oxygenase: molecular cloning and expression of a unique enzyme that oxidizes myo-inositol and D-chiro-inositol.

myo-Inositol oxygenase (MIOX) catalyses the first committed step in the only pathway of myo-inositol catabolism, which occurs predominantly in the kidney. The enzyme is a non-haem-iron enzyme that catalyses the ring cleavage of myo-inositol with the incorporation of a single atom of oxygen. A full-length cDNA was isolated from a pig kidney library with an open reading frame of 849 bp and a corresponding protein subunit molecular mass of 32.7 kDa. The cDNA was expressed in a bacterial pET expression system and an active recombinant MIOX was purified from bacterial lysates to electrophoretic homogeneity. The purified enzyme displayed the same catalytic properties as the native enzyme with K(m) and k(cat) values of 5.9 mM and 11 min(-1) respectively. The pI was estimated to be 4.5. Preincubation with 1 mM Fe(2+) and 2 mM cysteine was essential for the enzyme's activity. D-chiro-Inositol, a myo-inositol isomer, is a substrate for the recombinant MIOX with an estimated K(m) of 33.5 mM. Both myo-inositol and D-chiro-inositol have been implicated in the pathogenesis of diabetes. Thus an understanding of the regulation of MIOX expression clearly represents a potential window on the aetiology of diabetes as well as on the control of various intracellular phosphoinositides and key signalling pathways.

Simultaneous bilateral central retinal vein occlusion associated with anticardiolipin antibodies in leukemia.

PURPOSE: To present a dramatic case of simultaneous bilateral central retinal vein occlusion associated with leukemia and anticardiolipin autoantibodies. METHODS: Interventional case report. Clinical examination, fluorescein angiography, B-mode ultrasonography, and laboratory serologies were performed on a 65-year-old man with chronic myelogenous leukemia who presented with sudden onset of decreased vision in his right eye. RESULTS: Fundus examination disclosed a nonischemic central retinal vein occlusion. Over the next 3 weeks, a nonperfused central retinal vein occlusion developed in both eyes and subsequent neovascular glaucoma developed in his left eye. Throughout this time, his white blood cell and platelet counts remained normal and his serum viscosity remained low, but anticardiolipin antibodies were increased. CONCLUSION: This case reveals the occurrence of simultaneous bilateral central retinal vein occlusion associated with anticardiolipin antibodies in leukemia and suggests an additional mechanism other than hyperviscosity for bilateral central retinal vein occlusions in leukemic patients.

Paraneoplastic hypercalcemia in a patient with adenosquamous cancer of the colon.

Hypercalcemia is a well-known manifestation of paraneoplastic syndromes associated with a variety of malignancies. However, colon cancer has only rarely been associated with hypercalcemia of malignancy. We present the case of a patient with recurrent adenosquamous carcinoma of the ascending colon found to have hypercalcemia. The patient is a 76-year-old white woman who initially presented with colon cancer in the cecum and underwent a right hemicolectomy. All lymph nodes and surgical margins were free of tumor. Pathological examination at that time revealed adenosquamous carcinoma of the colon. Eight months later she complained of dizziness, anorexia, and constipation and was found to have a calcium level of 13.6 mg/dL. CT scan revealed a mass measuring 10.5 to 12.7 cm in the right hepatic lobe, and a bone scan was normal. Her intact parathyroid hormone (PTH) level was 6 pg/mL (normal 12-72) and her PTH-related protein (PTHrP) level was 25.7 pmol/L (normal <1.3). She then underwent a hepatic resection. The serum PTH, calcium, and PTHrP levels normalized after resection. Hypercalcemia of malignancy in colon cancer is rare and has an association with adenosquamous histology. The hypercalcemia is attributed to PTHrP, and here we demonstrate this in the serum and tumor specimens. The effects of PTHrP are shown to be short-lived postoperatively. We find only 14 other cases in the literature of hypercalcemia related to a colonic neoplasm, and this is the only patient reported to be surviving. The diagnosis of a paraneoplastic syndrome mediated via PTHrP should be considered when hypercalcemia is encountered in the setting of metastatic colon carcinoma.

Retinal pigment epithelial tear after transpupillary thermotherapy for choroidal neovascularization.

PURPOSE: To describe two patients who developed a retinal pigment epithelial tear after transpupillary thermotherapy for choroidal neovascularization. METHOD: Case reports. RESULTS: Retinal pigment epithelial (retinal pigment epithelium) tear developed in 2 (8%) of 25 eyes after transpupillary thermotherapy for occult choroidal neovascularization associated with age-related macular degeneration. In both eyes, the retinal pigment epithelium tear developed between the treatment session and first post-treatment examination. In both eyes, the visual acuity was unchanged, but the complication of retinal pigment epithelium tear may result in decreased visual acuity when transpupillary thermotherapy is performed in an eye with good initial visual acuity. CONCLUSION: Retinal pigment epithelium tear appears to occur more frequently after transpupillary thermotherapy for poorly defined choroidal neovascularization than after conventional laser photocoagulation for poorly defined choroidal neovascularization.

Macular hole surgery in high myopia.

PURPOSE: To evaluate the anatomic and functional outcomes of macular hole surgery in high myopia and to determine whether surgery is beneficial in myopic eyes with macular holes. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty eyes of 18 highly myopic subjects who underwent pars plana vitrectomy for macular holes. METHODS: We analyzed demographics, preoperative, and postoperative characteristics in 20 eyes with macular holes with a mean of 10.4 months duration and myopia of 6 diopters or greater. MAIN OUTCOME MEASURES: Macular hole closure rate and mean visual acuity preoperatively and postoperatively. RESULTS: Mean subject age was 56.4 years and preoperative visual acuity was 20/100+2. The macular hole was closed with one surgery in 60.0% of eyes and in 85.0% of eyes with one or more surgeries. The mean final acuity in all eyes was 20/63, and 40.0% improved greater than three Snellen lines at the final visit. The use of adjunctive agents seemed to have no effect on macular hole closure or visual acuity. A subgroup of three myopic eyes with retinal detachments surrounding the macular hole had successful closure with visual acuity improvement in two of three eyes. CONCLUSIONS: Macular hole surgery can give substantial visual improvement in myopic eyes with macular holes, but the anatomic closure rates are lower than in eyes with idiopathic macular holes, and thus a higher reoperation rate is required.

Results of macular hole surgery in patients over 80 years of age.

PURPOSE: To evaluate the results of macular hole surgery in patients over 80 years of age to determine if surgery is beneficial in an elderly patient population. METHODS: Twenty consecutive patients over age 80 with idiopathic macular holes and 20 nonconsecutive controls younger than 80 years treated for idiopathic macular holes were compared in a retrospective, consecutive case-control series. RESULTS: The macular hole was closed 3 months after surgery in 19/20 eyes (95%) of patients over age 80 years and 17/20 eyes (85%) of patients under 80 years. The mean preoperative visual acuity was 20/160 in patients over 80 years and 20/160-1 in patients under 80 years. The mean visual acuity at 3 months was 20/63 in eyes of patients over 80 years and 20/80 in eyes of patients under 80 years (P = 0.3). The mean visual acuity was 20/50-2 in eyes of patients over 80 years and 20/63-2 in eyes of patients under 80 years at the final examination (P = 0.403). CONCLUSIONS: Macular hole surgery is beneficial in patients over 80 years of age, with very similar results to those of patients younger than 80 years of age. Age should not be the primary criterion for recommending macular hole surgery.

Surgical treatment of macular holes with multiple recurrences.

PURPOSE: To evaluate the results of a third macular hole surgery in eyes with recurrent macular holes and two prior macular hole surgeries. DESIGN: Retrospective consecutive noncomparative case series. PARTICIPANTS: Sixteen eyes of sixteen patients with two prior macular hole surgeries with recurrent macular hole. INTERVENTION: A third vitreous surgery was performed in each eye using a long-acting gas bubble. MAIN OUTCOME MEASURE: Closure of the macular hole and change in visual acuity. RESULTS: The macular hole was closed in 12 of 16 eyes (75%) at 3 months after the third surgery. Visual acuity improved 2 or more Snellen lines in 9 of 16 eyes (56%), and 5 of 16 eyes (31%) achieved 20/40 or better vision. Six eyes (37.5%) had cataract surgery after the third macular hole surgery, and visual acuity results were similar in eyes with or without cataract surgery. Successful closure of the macular hole improved the visual acuity from 20/80 -1 to 20/50 +1 (P < 0.001). Eyes in which one of the previous surgeries had been temporarily successful in closing the macular hole improved from a mean of 20/80 to 20/40 (P = 0.003). Eyes in which both prior macular hole surgeries had been primary failures had minimal benefit with a preoperative visual acuity of 20/100 +1 and a postoperative visual acuity of 20/100 +2 (P = 0.67). CONCLUSIONS: Repeat macular hole surgery should be considered in eyes with recurrent macular holes and two prior surgeries when the macular hole was temporarily closed by at least one of the two previous surgeries. Successful closure of a macular hole in such cases usually results in significant visual acuity improvement.

Ulnar neuropathy as a complication of macular hole surgery.

OBJECTIVE: To report a series of patients manifesting ulnar neuropathy as an extraocular complication following macular hole surgery and facedown positioning. METHODS: Retrospective chart review of 7 patients identified by the operating surgeon as developing ulnar neuropathy during the immediate postoperative period after undergoing vitrectomy surgery with fluid-gas exchange for macular hole followed by at least 1 week of strict facedown positioning. RESULTS: All 7 patients developed symptoms of ulnar neuropathy, including paresthesias, dysesthesias, pain, weakness, and muscle atrophy. Signs included abnormal electromyogram, prolonged nerve conduction velocities, and impaired neurologic clinical test results in patients examined. Symptoms did not resolve with cessation of facedown positioning, and with follow-up ranging from 3 to 24 months all patients had persistent symptoms. All patients had positioned themselves with their arms continuously flexed. Three of 7 patients had placed pressure directly on their bent elbows. CONCLUSIONS: Ulnar neuropathy is an extraocular complication of macular hole surgery that can be attributed to arm position during postoperative facedown positioning. Surgeons performing macular hole surgery should caution their patients to minimize the amount of time spent with their elbows in a flexed position. Particular effort should be made to minimize pressure on the bent elbow.

F1-ATP synthase beta-subunit and cytochrome c transcriptional regulation in right ventricular hemodynamic overload and hypertrophically stimulated cardiocytes.

Cardiac hypertrophic growth secondary to hemodynamic pressure overload causes changes in energy requirements that may involve the transcriptional upregulation of oxidative phosphorylation genes. Therefore, two representative nuclear-encoded genes, the mitochondrial F1-ATP synthase beta-subunit (beta-subunit) and cytochrome c (cyt c), were examined in a feline chronic pulmonary artery banded right ventricular pressure-overload model. In the hypertrophying right ventricle, beta-subunit and cyt c mRNA levels increased after two and seven days, during the peak growth response. To examine cardiac transcriptional regulation, neonatal rat cardiac myocytes (cardiocytes) were transiently transfected with beta-subunit promoter constructs ranging from -1519 nucleotides (nt) upstream of transcription initiation as well as cyt c promoter constructs ranging from -726 nt. A full-length p1519beta-subunit/Luc construct was alpha-adrenergically inducible by 275% (+/-30%) with this activation being mapped to an enhancer region between -1519 to -1480 nt. Smaller constructs containing more proximal promoter elements were not inducible. Additionally, the full-length and enhancer deleted beta-subunit constructs were also inducible in electrically stimulated cardiocytes, suggesting a different mechanism of activation. Cyt c constructs containing known constitutive elements from -191 to -167 nt and -139 to -84 nt were responsible for the majority of the reporter activity of the full-length promoter but were not inducible in the presence of phenylephrine. Hence, we show that promoter regions containing elements common in other metabolism-related gene families are active in neonatal rat cardiocytes. Once more, we have identified a beta-subunit genomic region responsive to alpha-adrenergic and electrical stimulation.

Upregulation of the cardiac homeobox gene Nkx2-5 (CSX) in feline right ventricular pressure overload.

The recent characterization of the cardiac-specific homeobox gene Nkx2-5 (or CSX) and its detection in normal adult heart tissue raises the possibility of a role in adult hypertrophy. Using pressure overload as a primary stimulus, we used a feline pulmonary artery banding model to produce right ventricular hypertrophy (RVH). Total RNA was hybridized to a full-length murine Nkx2-5 cDNA probe that contained the NK family homeodomain. Nkx2-5 mRNA levels increased 5.1-fold (P < 0.05) and 3.9-fold vs. the corresponding left ventricles at 2 and 7 days of RVH, respectively, during the period of maximal myocardial growth. By 2 wk, when the RVH response had been completed, Nkx2-5 mRNA levels were returning toward baseline. Hybridization with an Nkx2-5 probe not containing the NK homologous homeodomain demonstrated that upregulation was specific for the Nkx2-5 gene. Atrial natriuretic factor and alpha-cardiac actin, both activated in part by Nkx2-5 DNA binding elements, also increased with RVH. These data suggest that a cardiac homeobox gene may play a role in the induction of adult cardiac hypertrophy.

Comparison of recombinant transforming growth factor-beta-2 and placebo as an adjunctive agent for macular hole surgery.

OBJECTIVE: This study aimed to compare the visual and anatomic results of macular hole surgery in eyes treated with recombinant transforming growth factor-beta-2 (TGF-beta2) or placebo. DESIGN: The design was a prospective, multicenter, randomized, double-masked, placebo-controlled clinical study. PARTICIPANTS: One hundred thirty eyes with idiopathic macular holes of 1 year or less and a refracted Early Treatment Diabetic Retinopathy Study visual acuity of 20/80 or worse were treated with 1.1 microg recombinant TGF-beta2 or placebo to the macular hole after fluid-gas exchange. INTERVENTION: The effect of recombinant TGF-beta2 as an adjunctive agent for macular hole surgery was evaluated. MAIN OUTCOME MEASURES: Closure of the macular hole and change in visual acuity at 3 months were measured. RESULTS: The 3-month visits were completed for 120 eyes. The macular hole was closed at 3 months in 35 (61.4%) of 57 eyes treated with placebo and 49 (77.8%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.08). The mean visual acuity gain was +6.4 letters in eyes receiving placebo and +8.9 letters in eyes treated with recombinant TGF-beta2 (P = 0.27). Visual acuity improved 2 or more lines in 23 (40.4%) of 57 eyes treated with placebo and 30 (47.6%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.42). Intraocular pressure elevation greater than 30 mmHg was more common 2 weeks after surgery in eyes treated with recombinant TGF-beta2 (P < 0.001). CONCLUSIONS: Recombinant TGF-beta2 resulted in a similar proportion of successful closure of macular holes as placebo. There was no statistically significant visual acuity benefit with the use of recombinant TGF-beta2 for the treatment of macular holes.

Reduction mammaplasty using the inferior pedicle technique.

A retrospective study of 350 reduction mammaplasties by the inferior pedicle technique performed over a 3-year period allows a critical evaluation of postoperative complications and patient satisfaction. The procedure can be done in a timely manner on an outpatient basis and is applicable to breasts of different shapes and sizes. The rate of postoperative complications (5%) was comparable with previous studies. Patient satisfaction was high (98%), with near-total relief of preoperative symptoms. Concern about the resultant scars was low (2%) when the incisions followed the natural contour of the breast.

Risk factors for elevated intraocular pressure after the use of intraocular gases in vitreoretinal surgery.

BACKGROUND AND OBJECTIVE: The authors studied the contribution of multiple factors, including gas type and concentration, to postoperative intraocular pressure (IOP) elevation following vitreoretinal surgery with intraocular gas. PATIENTS AND METHODS: One hundred seventy-one eyes of 134 patients were retrospectively investigated after vitreoretinal surgery using air, sulfur hexafluoride (SF6) (10%-30%), or perfluoropropane (C3F8) (5%-35%). RESULTS: IOPs greater than 25 mm Hg occurred in 74 of 171 eyes (43%). Elevated IOP was associated with increasing patient age (P < .001), expansile gas concentrations (P < .001), use of C3F8 (P = .01), and circumferential scleral buckles (P = .04). Most IOP elevations (65 eyes, 88%) occurred within 24 hours and responded to aqueous suppression within 24 to 72 hours. CONCLUSIONS: Transient IOP elevation is common following vitreoretinal surgery. Although it is responsive to treatment, it may pose a risk to some eyes. Prophylactic treatment should be considered in high-risk eyes.

The results of vitreous surgery for chronic macular holes.

PURPOSE: To evaluate the visual and anatomic results of macular hole surgery in eyes that have had symptoms of a macular hole for 2 years or longer. METHODS: Fifty-one eyes with chronic macular holes (> or = 2 years' duration) were treated in a retrospective analysis of the results of vitrectomy, 16% perfluoropropane gas tamponade, and one of three adjunctive agents (bovine transforming growth factor beta-2, recombinant transforming growth factor beta-2, or autologous platelet extract). Of 51 eyes, 45 (88.2%) were examined 3 months after surgery. Visual acuity of these 45 eyes was measured preoperatively and 3 months postoperatively using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. Twenty-eight eyes (62.2%) had no prior vitrectomy and 17 eyes (37.8%) had a prior vitrectomy for the macular hole that failed. RESULTS: The macular holes had a mean duration of 3.7 years and were successfully closed in 32 of 51 total eyes (62.7%) and 32 of 45 eyes (71.1%) that were examined 3 months after surgery. The mean preoperative visual acuity was 20/100 -2 and the mean visual acuity at 3 months was 20/80 for a mean gain of 6.6 ETDRS letters (+ 1.3 lines). Of 45 eyes, 17 (37.8%) were 20/63 or better 3 months after surgery; 21 (46.7%) gained 2 or more ETDRS lines. There was no statistically significant difference in macular hole closure (P = 0.311) or visual acuity change (P = 0.095) in eyes with or without prior vitreous surgery. Eyes with macular holes between 2-2.99 years experienced a somewhat better anatomic and functional result overall than eyes with macular hole from 3-14 years, duration, but the visual acuity change was not statistically significant (P = 0.187). There was substantial variability in visual improvement among eyes with successful closure of the chronic macular hole. CONCLUSIONS: Macular holes of > or = 2 years' duration may be more difficult to close successfully than are more recent macular holes, and the visual improvement appears to be less favorable. Many eyes with chronic macular holes in our study gained substantial visual acuity, so vitreous surgery can be considered in selected eyes with chronic macular holes based on visual needs.

Increased intraocular pressure after macular hole surgery.

PURPOSE: To determine the incidence and timing of increased intraocular pressure in eyes with an idiopathic macular hole treated with bovine transforming growth factor-beta 2 (TGF-beta 2) with different intraocular gas concentrations, recombinant TGF-beta 2, or placebo. METHODS: Intraocular pressure was measured preoperatively and two days, two weeks, six weeks, and three months postoperatively in two prospective studies of the treatment of idiopathic macular hole with vitrectomy. Group 1 consisted of 95 eyes treated with bovine TGF-beta 2. Eyes in this group were treated with different concentrations of air and perfluoropropane (C3F8) intraocular gas bubbles. Fifteen eyes were treated with air, 15 eyes with 5% perfluoropropane, 15 eyes with 10% perfluoropropane, and 50 eyes with 16% perfluoropropane. Group 2 consisted of 29 eyes treated with recombinant TGF-beta 2. Twenty-six eyes were treated with placebo in a double-masked, randomized, placebo-controlled study evaluating recombinant TGF-beta 2 with a 16% perfluoropropane intraocular gas bubble. RESULTS: At the two-week examination, the intraocular pressure in Group 1 eyes was > 30 mm Hg in four (26.7%) of 15 eyes treated with air, two (13.3%) of 15 eyes treated with 5% perfluoropropane, one (8.3%) of 12 eyes treated with 10% perfluoropropane, and nine (19.1%) of 47 eyes treated with 16% perfluoropropane. There was no statistically significant difference in the risk of increased intraocular pressure in eyes treated with short-, intermediate-, or long-duration gas tamponade using bovine TGF-beta 2. The intraocular pressure in Group 2 was > 30 mm Hg at the two-week examination in 11 (39.3%) of 28 eyes receiving recombinant TGF-beta 2 compared with one (4.3%) of 23 eyes receiving a placebo (P = .006). CONCLUSIONS: Some eyes develop increased intraocular pressure after vitreous surgery for macular hole, and the increase occurs most frequently between two days and two weeks postoperatively. The risk of increased intraocular pressure is somewhat increased in eyes treated with bovine TGF-beta 2 but is markedly increased in eyes in which recombinant TGF-beta 2 is used as an adjunctive agent for macular hole surgery. Intraocular injection of growth factors produced by similar recombinant DNA techniques may result in potentially dangerous increased intraocular pressure several weeks after surgery. Impurities in the recombinant TGF-beta 2 may explain the relatively high risk of increased intraocular pressure.