Martina M. Bosch

A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction.

Background. A healthy cornea is reliant on a distinct population of stem cells (SC) that replace damaged or aging epithelium throughout life. Depletion of the SC pool or damage to the niche can result in a blinding and painful condition known as limbal-SC deficiency (LSCD). Although current treatment strategies for reconstituting the ocular surface for patients suffering LSCD are promising, they are complicated by transferring autologous or allogeneic progenitors in the presence of animal, human, and synthetic products. We report on the safe and efficacy of a unique autologous SC transfer technique that utilizes an Food and Drug Administration-approved contact lens (CL) as the SC substrate and carrier for patients with LSCD. Methods. Three patients with LSCD due to aniridia (n=1) and posttreatment for recurrent ocular surface melanoma (n=2) were included. Limbal (n=2) or conjunctival biopsies (n=1) were harvested and progenitors expanded ex vivo on therapeutic CLs in the presence of autologous serum. Cell-laden CLs were transferred to the patients corneal surface and clinical outcome measures were recorded (follow-up range, 8–13 months). Results. A stable transparent corneal epithelium was restored in each patient. There was no recurrence of conjunctivalization or corneal vascularization, and a significant improvement in symptom score occurred in all patients. Best-corrected visual acuity was increased in all eyes after the procedure. Conclusion. Ex vivo expansion of ocular surface epithelium in the presence of autologous serum and transplantation with the aid of a soft CLs is a promising new technique capable of achieving ocular surface rehabilitation.

Nocturnal periodic breathing during acclimatization at very high altitude at Mount Muztagh Ata (7,546 m)

RATIONALE Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m). OBJECTIVES To investigate whether periodic breathing persists during prolonged stay at very high altitude. METHODS A total of 34 mountaineers (median age, 46 yr; 7 women) climbed from 3,750 m within 19-20 days to the summit at 7,546 m. During ascent, repeated nocturnal recordings of calibrated respiratory inductive plethysmography, pulse oximetry, and scores of acute mountain sickness were obtained. MEASUREMENTS AND MAIN RESULTS Nocturnal oxygen saturation decreased, whereas minute ventilation and the number of periodic breathing cycles increased with increasing altitude. At the highest camp (6,850 m), median nocturnal oxygen saturation, minute ventilation, and the number of periodic breathing cycles were 64%, 11.3 L/min, and 132.3 cycles/h. Repeated recordings within 5-8 days at 4,497 m and 5,533 m, respectively, revealed increased oxygen saturation, but no decrease in periodic breathing. The number of periodic breathing cycles was positively correlated with days of acclimatization, even when controlled for altitude, oxygen saturation, and other potential confounders, whereas symptoms of acute mountain sickness had no independent effect on periodic breathing. CONCLUSIONS Our field study provides novel data on nocturnal oxygen saturation, breathing patterns, and ventilation at very high altitude. It demonstrates that periodic breathing increases during acclimatization over 2 weeks at altitudes greater than 3,730 m, despite improved oxygen saturation consistent with a progressive increase in loop gain of the respiratory control system. Clinical trial registered with www.clinicaltrials.gov (NCT00514826).

Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m.

Investigations studying the secretion of EPO (erythropoietin) in response to acute hypoxia have produced mixed results. Further, the errors associated with the various methods used to determine EPO are not well documented. The purpose of the current study was to determine the EPO response of 17 trained male subjects to either an acute bout of normobaric hypoxia (Hy; n = 10) or normoxia (Con; n = 7). A secondary aim was to determine the error associated with the measurement of EPO. After baseline tests, the treatment group (Hy) underwent a single bout of hypoxic exposure (F(I(O(2))) approximately 0.148; 3100 m) consisting of a 90-min rest period followed by a 30-min exercise phase (50% V(O)(2max)). Venous blood samples were drawn pre (0 min) and post (120 min) each test to assess changes in plasma EPO (DeltaEPO). The control (Con) group was subjected to the same general experimental design, but placed in a normoxic environment (F(I(O(2))) approximately 0.2093). The Hy group demonstrated a mean increase in EPO [19.3 (4.4) vs. 24.1 (5.1) mU/mL], p < 0.04, post 120 min of normobaric hypoxia. The calculated technical error of measurement for EPO was 2.1 mU/mL (9.8%). It was concluded that an acute bout of hypoxia, has the capacity to elevate plasma EPO. This study also demonstrates that the increase in EPO accumulation was 2 times greater than the calculated measurement of error.

Use of Intraoperative Fourier-Domain Anterior Segment Optical Coherence Tomography During Descemet Stripping Endothelial Keratoplasty

PURPOSE To evaluate the intraoperative use of handheld Fourier-domain optical coherence tomography (OCT) during Descemet stripping automated endothelial keratoplasty (DSAEK) to assess the donor-host interface. DESIGN Prospective, observational case series. METHODS Six patients undergoing DSAEK surgery were included. OCT scans of the cornea were performed intraoperatively after insertion of the donor disc, after instillation of air in the anterior chamber beneath the disc, after vent incisions in the host cornea in each quadrant, following air-fluid exchange at the end of operation, and on day 1 after surgery. The central 3 mm of each cornea was scanned. The broadest gap between donor and host cornea (interface space) was measured. RESULTS Adequate readings could be obtained from all patients without any complications. In 2 patients there was a decrease in the width of the interface space after each surgical step documented by the OCT scans. At the end of their operation, no interface space was detectable. In 2 patients, interface space disappeared after the vent incisions and did not reappear during the further course of the surgery. In further 2 patients the separation between the host and donor was still detectable at the end of the operation. All patients had no detectable interface gap on day 1. CONCLUSIONS Handheld anterior segment OCT can be used to assess the host-donor interface in lamellar corneal transplantation surgery. Donor adherence can occur in spite of residual interface space at the end of surgery. Further studies should be conducted to answer the question of which surgical steps are useful in assisting with donor adhesion.

New insights into ocular blood flow at very high altitudes

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

The visual impact of fractionated stereotactic conformal radiotherapy on seven eyes with optic nerve sheath meningiomas.

Background: Treatment of primary optic nerve sheath meningiomas (ONSMs) remains controversial. Although recent studies have suggested a favorable outcome of radiotherapy, controlled data on the efficacy of fractionated stereotactic conformal radiotherapy (SCRT) in primary ONSMs are still lacking. Methods: Seven eyes treated with SCRT (total dose: 54 Gy) were compared with six eyes that were not treated because of patient or physician preference. The indication for intervention was deterioration of visual function with or without imaging evidence of tumor progression. Patients with secondary ONSMs and those with neurofibromatosis type 2 were excluded. The mean follow-up period was 57 months for the treated eyes and 61 months for the untreated eyes. Results: Among the seven treated eyes, visual acuity improved in six, five of which sustained improvement of three or more Snellen lines. One eye deteriorated by two lines. Visual field improved in four eyes, remained stable in two, and deteriorated in one. Four untreated eyes showed worsening of visual acuity and two remained stable. Visual field deteriorated in three eyes and was stable in three. None of the untreated eyes experienced improvement in visual acuity or visual field. No complications of treatment were documented. Conclusions: In agreement with previous reports, these results indicate that SCRT is superior to observation in its impact on visual function in eyes with primary ONSMs.

High Incidence of Optic Disc Swelling at Very High Altitudes

OBJECTIVES To determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema. METHODS This multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores. RESULTS Sixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001). CONCLUSION Optic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.

Tunnelled versus straight intravitreal injection: intraocular pressure changes, vitreous reflux, and patient discomfort.

Purpose: To compare tunnelled scleral intravitreal injection with straight scleral intravitreal injection concerning short-term intraocular pressure (IOP) changes, occurrence and amount of vitreous reflux, and patient discomfort. Methods: Sixty patients were randomly allocated to two groups (tunnelled intravitreal injection and straight intravitreal injection). IOP was measured before and directly (<1 minute) after the injection of 0.05 mL of an antivascular endothelial growth factor agent and then every 5 minutes until IOP was <30 mmHg. Occurrence and amount of vitreous reflux were recorded. Patient discomfort during injection was assessed with a Wong-Baker faces pain rating scale. Results: IOP (mmHg ± SD) increased significantly directly after injection to 35.97 ± 8.13 (tunnelled intravitreal injection) and 30.19 ± 12.14 (straight intravitreal injection). These pressure spikes differed significantly between both groups (P = 0.01, mean difference: −7.11). Five minutes after injection, there was no significant difference in IOP increase between the groups. All IOP measurements were <30 mmHg after 15 minutes. Occurrence and amount of vitreous reflux were significantly higher with straight intravitreal injection. There was no significant difference in Wong-Baker faces pain rating scale score between both groups. Conclusion: Tunnelled intravitreal injection seems to be the technique of choice for low-volume intravitreal injection (0.05 mL). There is neither a difference in patient discomfort nor a difference in IOP increase 5 minutes after injection between both groups. Significantly less vitreous reflux with tunnelled intravitreal injection should lead to less postinjectional drug loss.

New Insights Into Changes in Corneal Thickness in Healthy Mountaineers During a Very-High-Altitude Climb to Mount Muztagh Ata

OBJECTIVE To investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT). METHODS Twenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO(2)) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m. RESULTS Central corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 microm. Mean CCT in group 2 increased from 534 to 563 microm (P = .048). The amount of decrease in SpO(2) paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO(2) and age. CONCLUSIONS Corneal swelling during high-altitude climbs is promoted by low SpO(2). Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness-related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.

Intraocular Pressure during a Very High Altitude Climb

PURPOSE Reports on intraocular pressure (IOP) changes at high altitudes have provided inconsistent and even conflicting RESULTS The purpose of this study was to investigate the effect of very high altitude and different ascent profiles on IOP in relation to simultaneously occurring ophthalmic and systemic changes in a prospective study. METHODS This prospective study involved 25 healthy mountaineers who were randomly assigned to two different ascent profiles during a medical research expedition to Mt. Muztagh Ata (7,546 m/24,751 ft). Group 1 was allotted a shorter acclimatization time before ascent than was group 2. Besides IOP, oxygen saturation (SaO(2)), acute mountain sickness symptoms (AMS-c score), and optic disc appearance were assessed. Examinations were performed at 490 m/1,607 ft, 4,497 m/14,750 ft, 5,533 m/18,148 ft, and 6,265 m/20,549 ft above sea level. RESULTS Intraocular pressure in both groups showed small but statistically significant changes: an increase during ascent from 490 m/1,607 ft to 5,533 m/18,148 ft and then a continuous decrease during further ascent to 6,265 m/20,549 ft and on descent to 4,497 m/14,750 ft and to 490 m. Differences between groups were not significant. Multiple regression analysis (IOP-dependent variable) revealed a significant partial correlation coefficient of beta = -0.25 (P = 0.01) for SaO(2) and beta = -0.23 (P = 0.02) for acclimatization time. DISCUSSION Hypobaric hypoxia at very high altitude leads to small but statistically significant changes in IOP that are modulated by systemic oxygen saturation. Climbs to very high altitudes seem to be safe with regard to intraocular pressure changes.