The reactivation time in the treatment of AMD: a forgotten key parameter?

OBJECTIVE: Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB). METHOD: Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method). RESULTS: Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ). CONCLUSION: There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.

Therapeutic benefit of melatonin in refractory central serous chorioretinopathy.

PURPOSE: To evaluate the efficacy and safety of melatonin for the treatment of chronic central serous chorioretinopathy (CSCR). METHODS: Prospective comparative case series. A total of 13 patients with chronic CSCR were treated for 1 month: 8 patients were treated orally with 3 mg melatonin t.i.d., and 5 with placebo. All patients had 20/40 or worse Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) in the affected eye or presented an incapacitating scotoma. Most of the patients had previous failed treatments for their condition. Observational procedures included ETDRS BCVA, and complete ophthalmic examination. Optical coherence tomography (OCT) was performed at day 1 and week 4. Fluorescein angiography was performed at baseline only for diagnostic purposes. Data were subjected to two-sample t-test statistical analysis. P-values of <0.05 were considered statistically significant. RESULTS: At 1-month follow-up, BCVA significantly improved in 87.5% of patients treated with melatonin (7 of 8 patients, P<0.05). All patients showed a mean significant reduction (P<0.01) of central macular thickness (CMT) when compared with the baseline, with 3 patients (37.5%) exhibiting complete resolution of subretinal fluid at 1-month follow-up. No significant side effects were observed. No changes in BCVA or CMT were noted in the control group. CONCLUSIONS: These results suggest that melatonin is safe, well tolerated, and effective in the treatment of chronic CSCR, as it significantly improved BCVA and CMT in patients with this pathology. Further evaluations with longer follow-up and a larger patient population are desirable.

Serum pyroglutamyl aminopeptidase activity: a promising novel biomarker candidate for liver cirrhosis.

OBJECTIVE: As a reflect of tissue damage, serum aminopeptidases have been proposed as biomarkers of various diseases. In order to search new serologic markers for liver cirrhosis we conducted a preliminary study in which we analyzed a broad range of aminopeptidase activities in serum of controls and patients diagnosed with pancreatitis, hepatitis, and liver cirrhosis without distinction among the etiological type or the degree of severity of each condition. METHODS: Alanyl-, arginyl-, glutamyl-, cystinyl- pyroglutamyl-, and aspartyl-aminopeptidase activities were analyzed fluorometrically, using aminoacyl-ß-naphthylamides as substrates. In addition, various parameters, such as alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, direct bilirubin, and gamma glutamyl transpeptidase were assayed as routine laboratory test for liver function. RESULTS: Compared with control group, alanyl- and arginyl-aminopeptidase activities increased nonspecifically in pancreatitis, hepatitis and liver cirrhosis, glutamyl- and cystinyl-aminopeptidases did not differ between groups and pyroglutamyl-aminopeptidase demonstrated that while pancreatitis and hepatitis did not differ between them and with controls, this activity decreased selectively in liver cirrhosis compared with all the rest of groups (p<0.001 vs. control and p<0.01 vs. pancreatitis and hepatitis). Aspartyl-aminopeptidase also decreased significantly (p<0.05) in liver cirrhosis compared with controls. Routine parameters for liver function test increased, as expected, in the three pathologies analyzed. CONCLUSIONS: Despite the heterogeneous composition of the three patient groups, the specific reduction of the levels of pyroglutamyl-aminopeptidase activity in serum of liver cirrhosis patients might be considered as a potential candidate to be included in a combination of markers for the diagnosis of this disease.

Radiation-induced DNA damage as a predictor of long-term toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy.

This 14-year-long study makes a novel contribution to the debate on the relationship between the in vitro radiosensitivity of peripheral blood lymphocytes and normal tissue reactions after radiation therapy. The aims were (1) to prospectively assess the degree and time of onset of skin side effects in 40 prospectively recruited consecutive patients with locally advanced breast cancer treated with a hyperfractionated dose-escalation radiotherapy schedule and (2) to assess whether initial radiation-induced DNA damage in peripheral blood lymphocytes of these patients could be used to determine their likelihood of suffering severe late damage to normal tissue. Initial radiation-induced DNA double-strand breaks (DSBs) were assessed in peripheral blood lymphocytes of these patients by pulsed-field electrophoresis. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity score. A wide interindividual variation was observed in toxicity grades and in radiation-induced DNA DSBs in peripheral blood lymphocytes (mean 1.61 +/- 0.76 DSBs/Gy per 200 MBp, range 0.63- 4.08), which were not correlated. Multivariate analysis showed a correlation (P < 0.008) between late toxicity and higher prescribed protocol dose (81.6 Gy). Analysis of the 29 patients referred to 81.6 Gy revealed significantly (P < 0.031) more frequent late subcutaneous toxicity in those with intrinsic sensitivity to radiation-induced DNA DSBs of >1.69 DSBs/Gy per DNA unit. Our demonstration of a relationship between the sensitivity of in vitro-irradiated peripheral blood lymphocytes and the risk of developing late toxic effects opens up the possibility of predicting normal tissue response to radiation in individual patients, at least in high-dose non-conventional radiation therapy regimens.

Plasma aminopeptidase activities in Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by a progressive motor disorder, but frequently is accompanied by autonomic symptoms such as hypotension. Together with the decrease of dopamine, significant decreases in aminopeptidase activities have been reported in PD brains. However, up to date there are no studies about changes of aminopeptidase activities in plasma of PD patients. We studied plasma activities of alanyl-, aspartyl-(AspAP), cystinyl-(CysAP) and glutamyl-aminopeptidase (GluAP) in two groups of subjects: control (n=41) and PD (n=48). Plasma activities of AspAP, CysAP, and GluAP showed significant decreases of 24.9% (p<0.05), 39.4% (p<0.01) and 33.3% (p<0.01), respectively, in PD group. These aminopeptidases are involved in the metabolism of circulating peptides such as the ones of the renin-angiotensin system. The importance of aminopeptidases in striatal dopamine content and in neuroendocrine system in PD is discussed.

Levels of HSP70 in HIV(+) patients in different viroimmunological states.

The aim of the study was to establish an association between the viroimmunological status of HIV positive patients and their levels of the 70-kD heat shock protein (Hsp70). The longitudinal retrospective case study involved 61 patients at the University Hospital in Granada (Spain) from 1999 to 2002. Twenty-five patients were viroimmunologically stable, while the other 36 patients had suffered virological failure. A minimum of three blood samples were taken at intervals of at least 3 months for the patients who were stable virologically and immunologically, whereas four samples were taken for the virological failure group: two previous to the onset of virological failure, a third corresponding to the time of virological failure, and a fourth at least 3 months after remission of virological failure. Blood samples were also obtained from 20 healthy control subjects; Hsp70 levels in all were determined by enzyme immunoassay. The mean concentration of Hsp70 was 145.4 ng/ml in the HIV-infected patients as opposed to 72.1 ng/ml in the controls. While the viroimmunologically stable group showed levels similar to those of the controls (66.5 ng/ml), the mean value of Hsp70 in the virological failure group was nearly four times as high (249.1 ng/ml), yet this difference was not statistically significant. The patients treated with reverse transcriptase inhibitors were found to have significantly higher levels of Hsp70 than the other subjects. The transformed variable Hsp70/CD4(+) presents less variability than the Hsp70 value itself, giving a higher degree of statistical significance, and may be considered a useful parameter for diagnostic, prognostic, and therapeutic management of HIV positive patients.

Intravitreal triamcinolone acetonide injection in blind painful eyes. Intraocular steroids as a treatment for blind painful red eyes.

PURPOSE: Phthisis bulbi results from different ocular conditions. We evaluated intravitreal triamcinolone acetonide as a treatment option in blind painful eyes. METHODS: Thirty-one patients with unilateral phthisis were randomly divided into two groups. Group A received 0.3 ml (12.5 mg) triamcinolone acetonide intravitreally and Group B 0.3 ml balanced salt solution after retrobulbar anesthesia. Treatment success was assessed by subjective response to pain and clinically by biomicroscopic evaluation of conjunctival congestion. Tonometry was done before and after treatment. Follow-ups were at 24 hours, 3 weeks, 3 and 6 months, and 1 and 2 years. RESULTS: Throughout the two-year follow-up, only two patients in Group A reported pain after the procedure and were retreated, one at week 4 and the other at week 7. Conjunctival congestion was significantly lower in Group A. Two patients with hypotony before treatment had normal tension after triamcinolone. All Group B patients were reinjected with triamcinolone because pain continued after balanced salt solution injection. No severe complications were found. CONCLUSIONS: Intravitreal triamcinolone acetonide may be effective and safe for treating blind painful eyes.

Small choroidal melanoma with massive extraocular extension: invasion through posterior scleral emissary channels.

Massive orbital extension arising from a small posterior pole uveal melanoma is rare. A 75-year-old male followed for an asymptomatic choroidal nevus developed a two and a half month history of mild decrease in visual acuity. Upon clinical examination minimal enlargement of the tumor with surrounding serous retinal detachment was observed. Pre-operative magnetic resonance imaging disclosed massive extrascleral extension. Histopathology revealed that the tumor was composed of spindle B malignant melanoma cells. Multiple serial sections of the entire tumor area failed to demonstrate permeation through scleral lamellae. Instead, peripapillary perivascular short posterior ciliary vessel invasion was observed. This route of dissemination may explain the rapid growth and clinically undocumented behavior of small malignant melanomas at this location.

Laser in situ keratomileusis for myopia and hyperopia using the Lasersight 200 laser in 300 consecutive eyes.

PURPOSE: To evaluate effectiveness, safety, predictability, and short-term stability of laser in situ keratomileusis (LASIK) using the LaserSight Compac-200 Mini excimer laser with software version 9.0, for all refractive errors. METHODS: One hundred fifty consecutive patients (300 eyes) that received bilateral LASIK for myopia, hyperopia, and astigmatism were studied prospectively. A new 9.0 software version applying a modified nomogram that takes advantage of bilateral surgery was used. Follow-up at 6 months was available for 267 eyes (89%). RESULTS: Six months postoperatively, 131 eyes (96.32%) in the low to moderate myopia group (-1.00 to -5.99 D; n=136) had a spherical equivalent refraction within +/-1.00 D, and 123 eyes (90.44%) were within +/-0.50 D of emmetropia. In the high to extreme myopia group (-6.00 to -25.00 D; n=114), 97 eyes (87.08%) had a spherical equivalent refraction within +/-1.00 D and 78 eyes (68.42%) were within +/-0.50 D of emmetropia. In the hyperopia group (+1.00 to +6.00 D; n=50), 44 eyes (88%) had a postoperative spherical equivalent refraction within +/-1.00 D, and 31 eyes (62%) were within +/-0.50 D of emmetropia. Mean change in spherical equivalent refraction at 6 months was less than -0.50 D in the low to high myopia groups and -1.16 +/- 0.55 D in the extreme myopia group. At 6 months follow-up, uncorrected visual acuity was 20/20 or better in 73 eyes (54%) in the low to moderate myopia groups and 21 eyes (18%) in the high to extreme myopia groups. In the hyperopia group at 6 months follow-up, uncorrected visual acuity was 20/20 or better in 31 eyes (62%) and 20/40 or better in 41 eyes (82%). Only two eyes had a temporary loss of two or more lines of spectacle-corrected visual acuity due to corneal folds that were surgically treated. Six months after LASIK, no eye had lost any lines of best spectacle-corrected visual acuity in this series. CONCLUSIONS: Our modified LASIK nomogram with the 9.0 software of the LaserSight 200 excimer laser (with a larger and smoother ablation pattern) resulted in safe and effective outcomes for the treatment of low to high myopia, astigmatism, and hyperopia.

Reproducibility of patellofemoral CT scan measurements.

At least seven parameters have been described for the measurement of patellofemoral malalignment on CT scanning; three of which measure lateral patellar tilt, two lateral patellar shift and two femoral trochlear dysplasia. We studied 22 knees in 18 patients complaining of patellofemoral pain in order to investigate the reproducibility of these methods. CT scans of the patellofemoral joint were performed in each knee at 0 degrees and 20 degrees of flexion. The seven parameters were recorded from each scan by three independent observers in a blind study. The reproducibility was studied by means of the intraclass correlation coefficient (ICC). Parameters measuring lateral patellar tilt showed excellent reliability (ICC>75%). The measurements of lateral patellar shift and femoral trochlear dysplasia showed a fair or poor correlation (ICC<75%). We suggest that parameters for measuring lateral patellar tilt only should be used from CT scanning when planning treatment for patello-femoral malalignment.

Experimental retinopathy of prematurity: angiostatic inhibition by nimodipine, ginkgo-biloba, and dipyridamole, and response to different growth factors.

PURPOSE: To investigate whether commonly used vasodilating drugs ameliorate angiogenesis in experimental retinopathy of prematurity (ROP), and to study the response of these drugs to different growth factors. METHODS: We used a rat and mouse model of oxygen-induced ischemic retinopathy. Animals were treated with nimodipine, gingko-biloba and dipyridamole intraperitoneally starting the day before exposure to room air (day 1). Controls were injected with vehicle solution only. Eyes were processed histopathologically with serial sections and neovascularization was measured by counting the nuclei within the retinal internal limiting membrane, by a masked observer. Retinal and vitreous tissues were assayed by ELISA for VEGF, PDGF and TGFbeta2. RESULTS: Nimodipine significantly inhibited the growth of new vessels in rats. The number of nuclei was 310 +/- 69 in the control group (n:14) and 121 +/- 53 in the treated ones (n:14), (p<0.0005). Similar results were found with ginkgo-biloba extracts: 344 +/- 53 (n:15) in controls, and 136 +/- 29 (n:11) in treated ones (p<0.0005), and with dipyridamole: 303 +/- 69 (n:13) in controls, and 131 +/- 48.5 in treated rats (p<0.0005). Results were similar in mice. 186 +/- 45 (n:7) nuclei counted in controls against 90 +/- 25 (n:6) for dipyridamole treated (p<0.0005); and 81 +/- 21 for ginkgo-biloba treated animals (p<0.0005). A gradual, very significant increase in VEGF values in response to relative hypoxia (room air) contrasted with the significant inhibition noted both with ginkgo-biloba extracts and dipyridamole. TGFbeta2 and PDGF both showed a gradual increase in relative hypoxia at days 2 and 4 of room air (p<0.0005). Treated animals showed marked inhibition of the three growth factors. CONCLUSIONS: All three drugs markedly inhibited angiogenesis in experimental ROP. Growth factors were elevated in hypoxic conditions. Treated animals showed significant decreases of PDGF, VEGF, and TGFbeta2 in retinal and vitreous tissues.

Factors associated with microalbuminuria in type 1 diabetes mellitus: a cross-sectional study.

In order to determine the prevalence of microalbuminuria in people with Type 1 diabetes mellitus (Type 1 DM) and identify factors associated with microalbuminuria, we studied 312 Type 1 DM patients attending in three hospitals in two Spanish regions over 6 months. Clinical characteristics, micro- and macro-vascular complications, blood pressure, 24-h urine albumin excretion, lipid profile, HbA1(c) levels, smoking habits, and family history of hypertension and diabetic nephropathy were recorded. Univariate analysis and multiple logistic regression were used to examine associations between these variables and the prevalence of microalbuminuria. We detected microalbuminuria in 29% of the patients. The prevalence of microalbuminuria was high during the second decade of diabetes and declined thereafter. Univariate analysis showed dyslipidaemia (P<0. 002), previously diagnosed hypertension (P<0.001), family history of hypertension (sibling alone P<0.006; mother alone P<0.05), family history of diabetic nephropathy (P<0.001), and laser-treated retinopathy (P<0.03) to be factors associated with the presence of microalbuminuria. Multiple logistic regression revealed an association between microalbuminuria and family history of nephropathy (OR 7.6, 3.6-16). In conclusion, in our sample the frequency of microalbuminuria seems to be related to the presence of dyslipidaemia, hypertension, and to a family history of hypertension or nephropathy.

[Bilateral surgery: an efficient manner of creating LASIK nomograms]. / Cirugía bilateral: el mejor modo de realizar nomogramas personalizados de LASIK.

OBJECTIVE: Taking advantage of bilateral surgery, an efficient and predictable manner of doing Laser-assisted-in situ keratomileusis (LASIK) nomograms, is described. METHODS: We used our current technique of nomogram development with an example to described it. To evaluate a change made in the software of our LaserSight excimer laser unit: sixteen consecutive patients, operated on bilaterally, by the same surgeon, within statistically similar clinical, refractive, and surgical settings, were randomized with different nomogram for the right (OD), with a newer ablation pattern randomized in the (OS) the older sequential. Pattern. (Sequential overlapping burns) The refractive results were studied for statistical significance at 4 weeks and 6 months. The data was analyzed, using a student T test and two way Anova. RESULTS: Pre-operative refractive data showed a mean sphere in OD of -10.917 +/- 1.749, and OS of -10.89 +/- 1.717, p < NS. The mean preoperative spherical equivalent OD was -9.81 +/- 1.62 and OS of -9.93 +/- 2.02, p < NS. Post-operative mean spherical equivalent at 4 weeks in OD was +1.54 +/- 1.52, and in OS was +0.43 +/- 1.9, p < 0.05. At 6 months OD randomized was of +1.20 +/- 1.24 and, OS sequential of +0.14 +/- 1.70, p < 0.05. On the cylinder component of the refraction the values were equally corrected at both time points with p < NS. CONCLUSION: In a small group of patients, one current technique we use for nomogram development is described. Having similar statistical parameters, a significant overcorrecting with the new randomized ablation was observed, when surgery is carried out bilaterally. The change to the nomogram need then to be applied, so final refractive results are equal or better than the previous older sequential pattern. Four weeks results appeared to be time enough, since no statistical difference were observed at 6 months.

Emotional distress and occupational burnout in health care professionals serving HIV-infected patients: A comparison with oncology and internal medicine services.

BACKGROUND: The present paper examines the levels of emotional distress and professional burnout among health care professionals working with HIV patients in two different settings, Infectious Disease (ID) Units and a Haemophilia (H) Unit, and compares them with those of professionals working in Oncology (O) or General Internal Medicine (IM) Units, all at public hospitals. METHODS: Cross-sectional anonymous survey assessing their psychological condition, occupational stress, work and social adjustment, and providing information about stressors, supports and coping methods, using the General Health Questionnaire, the Maslach Burnout Inventory, the Modified Social Adjustment Scale, and other self-administered instruments. RESULTS: Perceived stress was higher in both O and IM, and the number of stressful circumstances was especially higher in O. No significant differences in psychological morbidity were found among the groups, with these exceptions: a better status among the H staff, who also showed less overall burnout; emotional exhaustion was lower in both ID and H than in the two other groups; the ID staff showed less personal accomplishment. Using a multiple regression model, a series of variables - including work adjustment, social/leisure adjustment, and having chosen to work in their position - was able to predict outcome. CONCLUSIONS: Our results highlight the presence of substantial levels of emotional distress and work-related difficulties in a significant number of health care workers. The mental health services could play an important role in conducting further research in this field and in providing practical help to deal with staff's difficulties.

Laser in situ keratomileus using the LaserSight 200 laser: results of 950 consecutive cases.

PURPOSE: To examine the refractive outcome in 950 consecutive eyes having laser in situ keratomileusis (LASIK) by 1 surgeon with experience in keratomileusis. SETTING: Outpatient excimer laser surgical facility. METHODS: This study comprised 950 consecutive eyes of 475 patients having LASIK as a primary procedure with a LaserSight 200 excimer laser (8.51 software). A nasal hinged flap and a Chiron microkeratome were used. Preoperative cycloplegic refraction was done only in patients younger than 25 years and in all hyperopic cases. Subjective preoperative and postoperative manifest refractions were done after autorefractometry in all cases. In cases of hyperopia, the software was modified by adding 30% to the refractive error. Enhancement results are not included. RESULTS: Of the 950 eyes, 893 (94.00%) were myopic and 57 (6.00%), hyperopic. In the low myopia group (1.00 to 3.99 D) of 223 eyes (24.97%), mean spherical equivalents (SEs) were -2.90 D +/- 0.56 (SD) preoperatively, -0.46 +/- 0.6 D 3 months postoperatively, and -0.41 +/- 0.5 D 6 months postoperatively. In the moderate myopia group (4.00 to 5.99 D) of 205 eyes (22.96%), respective mean SEs were -4.90 +/- 0.7 D, -0.90 D +/- 0.9 D, and -0.67 +/- 0.7 D. In the high myopia group (6.00 to 9.99) of 266 eyes (25.30%), the respective means were -7.70 +/- 1.3 D, -0.76 +/- 0.99 D, and -0.60 +/- 0.8 D. In the extreme myopia group (10.21 to 30.00) of 199 eyes (22.28%), the respective means were -13.30 +/- 2.9 D, -1.30 +/- 1.4 D, and -1.13 +/- 1.3 D. For the entire myopic group, the mean astigmatism was +1.55 +/- 1.38 D, +1.09 +/- 0.92 D, and +0.87 +/- 0.77 D, respectively. The low hyperopia group (1.00 to 2.99 D) of 39 eyes (68.42%) had a mean preoperative SE of +1.80 +/- 0.59 D and mean postoperative SEs of +1.00 +/- 0.76 D at 3 months and +1.16 +/- 0.52 D at 6 months. The respective means in the moderate hyperopia group (3.00 to 6.00) of 18 eyes (31.57%) were +4.62 +/- 1.19 D, +3.71 +/- 1.12 D, and +4.00 +/- 1.07 D. CONCLUSIONS: Laser in situ keratomileus for myopia using the LaserSight 200 excimer laser was stable with time and safe for the correction of different degrees of myopia. In the hyperopic group, marked regression occurred in a large percentage of patients. Thus, we will not perform LASIK for hyperopia until the software improves.

Bilateral macular hemorrhage after laser in situ keratomileusis.

BACKGROUND: This is the first report of a bilateral submacular hemorrhage after LASIK surgery in an extreme myo pic patient. A 31-year-old man underwent bilateral surgery for correction of -16.75+0.75x70 degrees and -16.50+0.50x55 degrees. METHODS: Case report. RESULTS: One day after surgery the patient's uncorrected visual acuity was in the 20/50 range OU and by 17 days after surgery his visual acuity had declined to 20/200 range. Fundus examination showed multifocal subretinal macular and posterior pole hemorrhages. Fluorescein angiography showed some macular lesions compatible with lacquer cracks. CONCLUSIONS: Preoperative and postoperative fundus examination is important to detect this phenomenon. Patients should be informed of this rare complication.

Effects of topical diclofenac and prednisolone eyedrops in laser in situ keratomileusis patients.

PURPOSE: To compare the effects of a topical nonsteroidal anti-inflammatory agent, diclofenac, and prednisolone acetate on wound healing, postoperative inflammation, and other clinical parameters in laser in situ keratomileusis (LASIK) patients. SETTING: Fundación VER, Córdoba, Argentina. METHODS: Laser in situ keratomileusis for myopia was performed simultaneously in both eyes of 16 patients by 1 surgeon. Patients were prospectively randomized to receive diclofenac eyedrops in the right eyes and prednisolone acetate eyedrops in the left. Postoperatively, the drops were administered topically every 2 hours the first day, every 6 hours the first week, every 8 hours the second week, and once a day the fourth week. Preoperatively and at each postoperative visit, evaluation of visual acuity, slitlamp biomicroscopy, corneal topography, and clinical scoring (0-III) of pain and photophobia were done; epithelial interface opacities were objectively evaluated. Follow-up was at 24, 48, and 72 hours, 1, 2, and 3 weeks, and 1, 2, 3, and 6 months. A paired t test was used for statistical analysis. RESULTS: Mean age of the 16 patients was 29.4 years +/- 6.5 (SD). Preoperatively, mean spherical equivalent was -5.83 +/- 3.61 diopters (D) in the right eyes and -6.96 +/- 4.66 D in the left eyes. At 6 months postoperatively, it was -1.83 +/- 1.87 D and -1.88 +/- 2.13 D, respectively. In the first 24 hours, there were significant clinical symptoms in the diclofenac group. CONCLUSIONS: Wound healing was stable, with no regression, in the diclofenac and prednisolone groups. Both anti-inflammatory agents worked well in LASIK patients.

Hypoxia inducible factor-1alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression.

PURPOSE: Hypoxia inducible factor-1 (HIF-1) is a transcription factor composed of HIF-1alpha and HIF-1beta subunits. HIF-1 transactivates multiple genes whose products play key roles in oxygen homeostasis, including vascular endothelial growth factor (VEGF). This study was designed to determine whether HIF-1 levels are increased in ischemic retina and whether there is a correlation with increased expression of VEGF. METHODS: C57BL/6J mice were killed at time points that span retinal vascular development (PO to adult), or on postnatal day (P) 7 they were placed in a 75% oxygen environment for 5 days and then removed to room air and killed after 0, 2, or 6, or 24 hours and 5 or 14 days. Eyes were frozen, and retinas were isolated and used for immunoblot analysis, or eyes were sectioned for immunohisto chemical staining for HIF-1alpha or HIF-1beta, or for in situ hybridization for VEGF. RESULTS: Immunoblots of retinal lysates showed low levels of HIF-1alpha at PO that were markedly increased at P4, remained high throughout the period of retinal vascular development and then decreased to an intermediate level in adults. HIF-1beta levels were relatively constant at all time points. In mice with oxygen-induced ischemic retinopathy, HIF-1alpha levels were increased in the retina. The peak of increase occurred at 2 hours, and levels returned to baseline by 24 hours. Immunohistochemistry showed increased staining for HIF-1alpha throughout the hypoxic inner retina, but not in the normoxic outer retina. There was no modulation of HIF-1beta levels. There was constitutive expression of VEGF mRNA in the inner nuclear layer that was increased 6 hours after the onset of hypoxia and remained elevated for several days. CONCLUSIONS: There are increased levels of HIF-1alpha in ischemic retina that show temporal and spatial correlation with increased expression of VEGF. These findings are consistent with the hypothesis that HIF-1 plays a role in upregulation of VEGF in ischemic retina.

Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model.

Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast growth factor (FGF2) plays a role in stimulating CNV. In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CNV. One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV. At 2 weeks, CNV was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.