Long-term outcomes of Fine Needle Diathermy for established corneal neovascularisation.

BACKGROUND/AIMS: Corneal neovascularisation (CoNV) can lead to significant ocular comorbidity with reduction in vision and cosmesis. A number of techniques have been described to reduce CoNV, but these can be expensive. Our study aimed to determine the safety, efficacy and long-term outcomes of fine needle diathermy (FND) for CoNV. METHODS: A 5-year retrospective study identified all cases of FND. Indications, intraoperative complications, and postoperative visual acuity, after treatment and retreatments, were documented, along with the procedure time. Evidence of regression and number of retreatments were identified. RESULTS: 56 eyes from 52 patients underwent FND for CoNV. The main indications included herpes simplex keratitis (HSK) (53%, n=25) and microbial keratitis/peripheral ulcerative keratitis (13%, n=6). Pretreatment acuity was significantly correlated with extent of CoNV (p=0.044). One complication was noted during the procedure-an intrastromal and subconjunctival haemorrhage (rate 2%). 68.1% of patients demonstrated regression at first follow-up (mean 6.9 weeks), and 89.3% (n=42) showed regression with two or less treatments. Mean post-FND acuity was 0.72 (range -0.2-3.0) vs 0.82 (-0.2-3.0) preprocedure (p=0.08). VA improved in the HSK subgroup (p=0.012). Mean follow-up was 18.9 months (range 1-56 months). CONCLUSIONS: In the largest case series reported, FND appears to be a safe and effective technique in the long term to induce regression of CoNV, with significant improvement in the VA of patients with HSK.

The journey to femtosecond laser-assisted cataract surgery: new beginnings or a false dawn?

Femtosecond laser-assisted cataract surgery (FLACS) represents a potential paradigm shift in cataract surgery, but it is not without controversy. Advocates of the technology herald FLACS as a revolution that promises superior outcomes and an improved safety profile for patients. Conversely, detractors point to the large financial costs involved and claim that similar results are achievable with conventional small-incision phacoemulsification. This review provides a balanced and comprehensive account of the development of FLACS since its inception. It explains the physiology and mechanics underlying the technology, and critically reviews the outcomes and implications of initial studies. The benefits and limitations of using femtosecond laser accuracy to create corneal incisions, anterior capsulotomy, and lens fragmentation are explored, with reference to the main platforms, which currently offer FLACS. Economic considerations are discussed, in addition to the practicalities associated with the implementation of FLACS in a healthcare setting. The influence on surgical training and skills is considered and possible future applications of the technology introduced. While in its infancy, FLACS sets out the exciting possibility of a new level of precision in cataract surgery. However, further work in the form of large scale, phase 3 randomised controlled trials are required to demonstrate whether its theoretical benefits are significant in practice and worthy of the necessary huge financial investment and system overhaul. Whether it gains widespread acceptance is likely to be influenced by a complex interplay of scientific and socio-economic factors in years to come.

Insignificant response of the fetal placental circulation to arterial hypotension in sheep.

Infusion of the angiotensin-converting enzyme inhibitor enalaprilat into fetal sheep caused a profound arterial hypotension within days. Five fetal lambs were infused with enalaprilat for 8 days starting at day 128 of gestation. Total accumulated dose was 0.30 ± 0.11 mg/kg. Arterial pressure decreased from 43.6 to 25.6 mmHg; venous pressure did not change. Biventricular output was not statistically significantly changed; placental blood flow decreased almost in proportion to the decrease in pressure but the increase in somatic flow was not statistically significant. There were no significant changes in pressure 30 min after the initial 50-µg loading dose of enalaprilat. However, the arterial pressure responses to test doses of ANG I were largely abolished. After 1 day, however, there was a significant decrease in somatic vascular resistance, which became stronger with time, but almost no decrease in the placental resistance. We conclude that the fetal somatic circulation exhibits a slow but strong decrease in resistance but that the response to hypotension is weak or absent in the fetal placenta, possibly because it is already fully relaxed.

Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart.

The fetal heart is highly sensitive to changes in mechanical load. We have previously demonstrated that increased cardiac load can stimulate cell cycle activity and maturation of immature cardiomyocytes, but the effects of reduced load are not known. Sixteen fetal sheep were given either continuous intravenous infusion of lactated Ringer solution (LR) or enalaprilat, an angiotensin-converting enzyme inhibitor beginning at 127 days gestational age. After 8 days, fetal arterial pressure in the enalaprilat-infused fetuses (23.8 +/- 2.8 mmHg) was lower than that of control fetuses (47.5 +/- 4.7 mmHg) (P < 0.0001). Although the body weights of the two groups of fetuses were similar, the heart weight-to-body weight ratios of the enalaprilat-infused fetuses were less than those of the LR-infused fetuses (5.6 +/- 0.5 g/kg vs. 7.0 +/- 0.6 g/kg, P < 0.0001). Dimensions of ventricular myocytes were not different between control and enalaprilat-infused fetuses. However, there was a significant decrease in cell cycle activity in both the right ventricle (P < 0.005) and the left ventricle (P < 0.002) of the enalaprilat-infused fetuses. Thus, we conclude a sustained reduction in systolic pressure load decreases hyperplastic growth in the fetal heart.

Persistent changes in arterial blood gases in fetal sheep.

Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.

Propagation of fluctuations in biochemical systems, II: Nonlinear chains.

We consider biochemical reaction chains and investigate how random external fluctuations, as characterised by variance and coefficient of variation, propagate down the chains. We perform such a study under the assumption that the number of molecules is high enough so that the behaviour of the concentrations of the system is well approximated by differential equations. We conclude that the variances and coefficients of variation of the fluxes will decrease as one moves down the chain and, through an example, show that there is no corresponding result for the variances of the concentrations of the chemical species. We also prove that the fluctuations of the fluxes as characterised by their time averages decrease down reaction chains. The results presented give insight into how biochemical reaction systems are buffered against external perturbations solely by their underlying graphical structure and point out the benefits of studying the out-of-equilibrium dynamics of systems.

Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep.

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.

Correlation of long term phenotypic and clinical outcomes following limbal epithelial transplantation cultivated on amniotic membrane in rabbits.

AIM: To determine the epithelial phenotype in rabbits with total limbal stem cell deficiency (LSCD) after reconstruction with autologous limbal epithelial stem cells ex vivo expanded on rabbit amniotic membrane (AM). METHODS: Left eyes of 52 rabbits were rendered total LSCD, verified by impression cytology. The fibrovascular pannus of each cornea was removed. Group I (n = 10) received rabbit AM transplantation alone, while groups II-IV (n = 42) underwent transplantation of LSC cultured on rabbit AM (LSC-AM) from a small limbal biopsy taken from the right eye. Clinical outcome was graded as "success," "partial success," or "failure" depending on the corneal smoothness and avascularity. Epithelial phenotype was determined by immunostaining and graded as "corneal (K)," "conjunctival (J)," or "mixed (M)" depending on expression of K3 and Muc5AC. RESULTS: After 1 year follow up, group I showed 100% failure and groups II-IV showed 26% success (p<0.001). Clinical failure correlated with J phenotype p = 0.001), while clinical success correlated with K phenotype p = 0.01). When the phenotypic outcome was used for comparison, J phenotype was significantly high in group I (p = 0.003), while K phenotype was significantly high in groups II-IV (p<0.05). CONCLUSION: There is a strong correlation between clinical success and resultant corneal epithelial phenotype. Ex vivo expanded LSC can successfully reconstruct corneal surfaces with unilateral total LSCD.

Nedocromil sodium and levocabastine reduce the symptoms of conjunctival allergen challenge by different mechanisms.

BACKGROUND: Nedocromil sodium and levocabastine are widely used for the treatment of ocular allergy, but their mechanisms of action are unclear. OBJECTIVE: We sought to compare the efficacy and mechanisms of action of nedocromil sodium and levocabastine in reducing conjunctival symptoms after ocular allergen challenge. METHODS: We performed a double-blind, placebo-controlled study in which 48 subjects were randomized to 3 groups to receive nedocromil sodium (2%), levocabastine (0.05%), or placebo eye drops twice daily for 2 weeks before ocular challenge with 10 microL of ryegrass extract. Symptoms and tear histamine and PGD(2) concentrations were determined before challenge and at 10, 20, 30, 60, 180, and 360 minutes after challenge. Bulbar biopsy specimens were taken at 6 and 24 hours after challenge to assess conjunctival inflammatory cell numbers, adhesion molecule expression, and mast cell-associated IL-4, IL-5, IL-6, IL-13, and TNF-alpha levels. RESULTS: Both drugs significantly reduced total symptom scores (P <.05) at all times after challenge compared with placebo. Itching, hyperemia, and lacrimation were most affected. Nedocromil sodium treatment reduced tear concentrations of histamine (by 77%) and PGD(2) (by 70%) at 30 minutes after challenge (both P <.05). In biopsy specimens nedocromil sodium reduced the number of 3H4-positive mast cells (purportedly the secreted form of IL-4) by 49% at 6 hours and 59% at 24 hours (both P <.05). Levocabastine reduced intercellular adhesion molecule 1 expression by 52% at 6 hours and 45% at 24 hours (both P <.05). CONCLUSION: Nedocromil sodium and levocabastine both reduced the conjunctival symptoms after ocular allergen challenge but appeared to work by different mechanisms. Nedocromil sodium reduced mast cell function, whereas levocabastine appeared to have primarily antihistaminic actions, although it also reduced the expression of intercellular adhesion molecule 1.

Amniotic membrane transplantation after the primary surgical management of band keratopathy.

PURPOSE: To determine the safety and efficacy of amniotic membrane transplantation to restore and maintain a stable corneal epithelium and reduce ocular surface pain after surgical removal of band keratopathy arising from ocular causes. METHODS: Fifteen patients (16 eyes) from two centers with band keratopathy secondary to ocular causes underwent amniotic membrane transplantation as a graft after surgical removal of calcific deposits with or without the use of ethylenediaminetetraacetic acid. In a prospective, consecutive, uncontrolled case series, the rate of corneal epithelialization and resultant surface stability were recorded over a mean follow-up period of 14.6 months. RESULTS: Pain from ocular surface instability was the presenting complaint in 14 of 15 (93.3%) patients and resolved in all cases after the procedure even for those who experienced a recurrence of the calcific deposit. Fifteen of 16 eyes (93.7%) achieved epithelialization with a mean time to epithelial healing of 15.2 days. The only eye that failed to heal was subsequently diagnosed with total limbal stem cell deficiency. Visual acuity improved in five of nine (44%) sighted eyes and remained unchanged in four of nine (56%). No patient experienced any major surgical or medical complication after the procedure. CONCLUSION: Amniotic membrane transplantation represents a safe and effective method to restore a stable corneal epithelium in eyes after primary surgical removal of band keratopathy arising from ocular causes.

Amniotic membrane transplantation for partial limbal stem cell deficiency.

AIM: To examine the efficacy, safety, and long term outcomes of amniotic membrane transplantation for corneal surface reconstruction in cases of partial limbal stem cell deficiency. METHODS: 17 eyes of 15 patients with partial limbal stem cell deficiency underwent superficial keratectomy of the conjunctivalised corneal surface followed by amniotic membrane transplantation. Cases were followed up for at least a year. RESULTS: All eyes exhibited a stable, intact corneal epithelial surface after a mean follow up period of 25.8 months with no eyes developing recurrent erosion or persistent epithelial defect. The mean time to re-epithelialisation was 22.8 days. Overall improvement in visual acuity was observed in 92.9% of 14 eyes with visual potential. Of those, five eyes gained six or more lines, two eyes gained between four and five lines, six eyes gained between one and three lines, and one eye lost three lines of Snellen acuity. Pain and photophobia were abolished in 86% of cases and substantially reduced in 14%, with all eyes exhibiting decreased vascularisation and inflammation at final follow up. CONCLUSIONS: Amniotic membrane transplantation appears to be a safe and effective method of restoring a stable corneal epithelium for cases of partial limbal stem cell deficiency and can be considered as an alternative to limbal autograft or allograft.

The relative contribution of mast cell subsets to conjunctival TH2-like cytokines.

PURPOSE: To investigate the distribution of the T-helper (TH)2-like cytokines, interleukin (IL)-4, IL-5, IL-6, and IL-13 between mast cell subsets in conjunctival biopsy specimens from normal subjects and those with seasonal allergic conjunctivitis (SAC) during and outside of the grass pollen season. METHODS: Sequential and double in situ hybridization (ISH) and immunohistochemistry (IHC) were performed on thin sections of human conjunctiva to determine the colocalization of the immunoreactivity of IL-4, IL-5, IL-6, and IL-13 to mast cell subsets in normal subjects and subjects with atopy and to detect IL-4 mRNA in conjunctival mast cells. RESULTS: More than 90% of IL-4+-immunoreactive cells were observed to be mast cells in conjunctival biopsy specimens from all patient groups. The majority of IL-5+, IL-6+, and IL-13+ cells were also noted to be mast cells for each group. IL-4 preferentially colocalized to the tryptase+-chymase+ mast cell phenotype (MC(TC)) with MC(TC) cells comprising 93.3% of cytokine+ mast cells in symptomatic SAC (P = 0.0017), 89.2% in asymptomatic SAC (P = 0.0008), and 77.8% in normal subjects (P = 0.0472). IL-13 appeared to colocalize preferentially to the MC(TC) phenotype and IL-5 and IL-6 to the MC(T) phenotype. ISH showed that 75.8% of mast cells in normal subjects, 78.7% in subjects with symptomatic SAC, and 18.7% in subjects with asymptomatic SAC expressed mRNA for IL-4. CONCLUSIONS: Conjunctival mast cells are an important source of IL-4, IL-5, IL-6, and IL-13 immunoreactivity, with preferential colocalization of IL-4 and IL-13 on the MC(TC) subset and IL-5 and IL-6 to the MC(T) subset. This evidence suggests that differences in protease phenotype may also reflect functional differences evidenced by the different patterns of cytokine distribution.

Non-communication between ophthalmologists and optometrists.

Many patients seen in the British hospital eye service are referred by high-street optometrists; and, if the optometrist is to receive feedback from the ophthalmologist, the patient should consent to disclosure of medical information. On the referral form (revised GOS 18) there is a space for this purpose. We investigated the level of communication by asking optometrists in our hospital catchment area about their use of the GOS 18 form and by examining the medical records of all new patients seen in the eye outpatient department in one month. 79 optometrists (55%) returned the questionnaire. 54 routinely used the GOS 18; and, of these, 10 said they obtained patient consent always, 23 sometimes and 21 never. 158 of 555 sets of medical notes contained an optometrist's referral, 107 of them on the revised GOS 18; and patient consent had been recorded on 17 of these forms. Ophthalmologists responded to the optometrist in 2/17 (12%) cases where consent had been obtained and 15/90 (17%) where it had not. Ophthalmologists could provide much better feedback to optometrists. The GOS 18 form could be used more effectively; and there is no reason why patient consent to disclosure of medical information should not be obtained by ophthalmologists as well as by optometrists.

Regulatory response of intramembranous absorption of amniotic fluid to infusion of exogenous fluid in sheep.

Six fetal sheep were operated on at 118 to 121 days of gestation. The pulmonary end of the trachea was connected to the gastric end of the esophagus with a section of tubing. This left urine as the only source of amniotic fluid and intramembranous absorption as sole exit. Multiple indwelling fetal vascular, intra-amniotic, allantoic, and a fetal bladder catheter were placed. Beginning 5 days after surgery, all urine was drained from the bladder and immediately reinfused into the amniotic sac to monitor urine production rate. After 4 days of urine infusion alone, the urine infusion was augmented for 6 days with an intra-amniotic infusion of Ringer solution. Amniotic and allantoic fluid volumes were measured at autopsy. During the period of Ringer infusion, intramembranous absorption of amniotic fluid increased by more than 1,191 +/- 186 (SE) ml/day (P < 0.002) and the rates of Na(+) and Cl(-) absorption increased to more than five times (P < 0.005) and eight times (P < 0.005) their initial values. Only one of six fetuses had polyhydramnios. It is concluded that intramembranous absorption of amniotic fluid makes a strong regulatory adjustment in response to an abnormal increase in inflow of exogenous fluid.