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[Treatment of retinal detachment with intraocular expandable gas injection].

The injection of expandable gas into the vitreous is a new method for treating retinal detachment. The injected gas bubble seals the retinal break and allows absorption of subretinal fluid. In 12 patients, in all eyes treated by injection of sulfur hexafluoride, the detached retina became reattached. In 3 eyes (25%) detachment recurred. To achieve attachment again, both vitrectomy and the circling band operation were performed in 2 of them, and only the latter operation in the third. Risk factors for redetachment included detachment of the macula, retinal detachment larger than 5-o'clock-hours, and pseudophakia. Proper selection of patients for gas injection is most important.

Gases↗

Carbonic anhydrase inhibitors. metal complexes of 5-(2-chlorophenyl)-1,3,4-thiadiazole-2-sulfonamide with topical intraocular pressure lowering properties: the influence of metal ions upon the pharmacological activity.

Metal complexes of a sulfonamide possessing strong carbonic anhydrase (CA) inhibitory properties, 5-(2-chlorophenyl)-1,3,4-thiadiazole-2-sulfonamide (chlorazolamide) have been obtained from the sodium salt of the sulfonamide and the following metal ions: Mg(II), Zn(II), Mn(II), Cu(II), Co(II), Ni(II), Be(II), Cd(II), Pb(II), Al(III), Fe(III) and La(III). The original sulfonamide and its complexes were assayed for the in vitro inhibition of three CA isozymes, CA I, II, and IV, some of which play a critical role in ocular fluid secretion. All these compounds (the sulfonamide and its metal complexes) behaved as powerful inhibitors against the three investigated isozymes. The parent sulfonamide possessed an extremely weak topical pressure lowering effect when administered as a 1-2% suspension into the rabbit eye, but some of its metal complexes, such as the Mg(II), Zn(II), Mn(II) and Cu(II) derivatives, lower intraocular pressure (IOP) in experimental animals very well. Ex vivo data showed a 99.5-99.9% CA II inhibition in ocular fluids and tissues of rabbits treated with these agents, proving that the observed IOP lowering is due to CA inhibition. The influence of the different metal ions upon the efficiency of the obtained complexes as pressure lowering drugs are discussed, leading to the possibility of designing more selective/potent pharmacological agents from this class.

Animals↗

Differential elasticity of the immature retina: a contribution to the development of the area centralis?

Differential stretch of a retinal surface with an initially uniform cell density has been repeatedly implicated as one of the developmental mechanisms that produces the topographic organization of cell density in the adult retina, notably the area centralis or visual streak versus peripheral regions. It is known that intraocular pressure is required to produce the normal conformation and thinning of the retina during development. We tested the possibility that the retina has elastic properties that might permit differential stretch in conjunction with intraocular pressure. The relative deformation of the retina containing the presumptive area centralis was compared to the deformation of peripheral retina at equivalent applied fluid displacements in 7-12-day-old cats. The peripheral retina deformed significantly more, consistent with the hypothesis that differences in the local elasticities of the developing neural retina contribute to its characteristic topographic changes. Thus, a biomechanical property of the growing eye may contribute to the mechanism by which the pattern of the visual array is sampled.

Animals↗

The natriuretic peptides: universal volume controllers.

Since the discovery of the natriuretic effect of atrial natriuretic peptide (ANP), a family of other natriuretic peptides similar to ANP were isolated, including atriopeptin, vessel dilator, long-acting natriuretic peptide, urodilatin, and brain natriuretic peptide (BNP) to name a few. ANP was noted to possess natriuretic and diuretic properties that controlled increases in intravascular volume. ANP was also found to be elevated in conditions of increased intraocular pressure and biliary obstruction. BNP was found to be elevated in conditions of increased intracranial pressure, pointing towards its role in controlling cerebrospinal fluid volume. While at the cellular level, ANP controlled individual cell size. This makes the natriuretic peptides not only controllers of intravascular volume, but also modulators of a myriad of cavity volumes down to the control of individual cell volume.

Atrial Natriuretic Factor↗

[Clinical value of multifrequential tympanometry].

Multi-frequency tympanometry brings into evidence, in the normal subject, three types of tympanogram of acoustic impedance. The frequency of the tone probe showing a W tympanogram seems to be the key element. This frequency is close to that of the resonance of the ear, which is altered in the case of pathology of the tympano-ossicular system and of increase in the pressure of the endolabyrinthine fluids. Multi-frequency tympanometry facilitates the differential diagnosis between ankylosis and a discontinuity of the ossicular chain. It also objectifies the variations in the pressure of the inner-ear fluids in Ménière's disease.

Acoustic Impedance Tests↗

[Vitrectomy in the treatment of ocular trauma].

74 cases of ocular trauma comprised traumatic cataract in 9 eyes, traumatic vitreous opacity in 23 eyes, traumatic retinal detachment in 29 eyes, intraocular foreign bodies in 11 eyes, and traumatic endophthalmitis in 2 eyes. Operations of closed vitrectomy, scleral buckling, lensectomy with vitrectomy and gas-fluid exchange effected vitreous clarity in 69 eyes (93.2%) and visual improvement in 52 eyes (70.3%). Surgical complications occurred in 8 eyes (10.8%).

Adolescent↗

Cerebrospinal fluid formation in rats and cats during treatment with timolol.

The influence of timolol upon cerebrospinal fluid formation rate has been examined in rats by the measurement of 22Na+ entry into this fluid after 10, 100, or 1000 micrograms x kg-1 i.v. and in cats by the dye-dilution measurement of new fluid formation after 30, or 3000 microgram x kg-1 i.v., or 250 micrograms x mL-1 in ventricular perfusate. In rats no change from control rates occurred. In the cats there appeared to be no effect of intraventricular timolol; however, a significant decrease of approximately 25% in the mean flow rate was seen after 40 min when drug was given i.v. at either dose level. A time study showed that no further decrease occurred within 5 h and that the observed decrease continued for at least 3 h. These findings are of interest in view of the ability of topical, intraocular, and i.v. timolol to reduce aqueous humor formation rate.

Animals↗

Evidence that peritoneal exudate cells cultured with eye-derived fluids are the proximate antigen-presenting cells in immune deviation of the ocular type.

Immune privilege in the anterior chamber of the eye results in part from a selective deficit in delayed hypersensitivity that is elicited by antigenic materials placed in this unique tissue site. This distinctive systemic immune response to intraocular Ag (termed anterior chamber-associated immune deviation, ACAID) is fashioned by indigenous, intraocular bone marrow-derived cells that capture Ag within the anterior chamber and carry an Ag-specific ACAID-inducing signal via the blood directly to the spleen. An identical form of immune deviation can be evoked by the i.v. injection of peritoneal exudate cells (PEC) pulsed in vitro with soluble Ag in the presence of transforming growth factor-beta (TGF-beta). To determine whether eye-derived cells present Ag directly to responding splenic T cells or merely serve as vehicles to deliver Ag to the spleen, we have conducted MHC restriction experiments with PEC donors and recipients selected to differ at loci dictating MHC and/or minor histocompatibility Ag. When PEC were pulsed in vitro with soluble Ag (BSA) in the presence of culture fluid containing TGF-beta and injected into recipients with which they shared either class I or class II MHC molecules, BSA-specific ACAID was induced. By contrast, PEC pulsed with BSA and TGF-beta-containing culture fluid failed to induce ACAID when the cells were injected into recipients who were completely histoincompatible or were identical with the injected cells only at non-MHC loci. Using MHC class I-deficient transgenic mice, it was determined that intraocular injection of BSA failed to induce ACAID, and that class I-deficient PEC were incapable of inducing either BSA-specific ACAID or splenic regulatory T cells that suppress BSA-specific delayed hypersensitivity. We conclude that cells that carry an ACAID-inducing signal to the spleen are: 1) restricted in their ability to induce ACAID by MHC-encoded molecules, 2) these cells are the proximate APC ACAID, and 3) class I MHC molecules play a central role in presenting exogenous protein Ag to splenic T cells in ACAID.

Animals↗

Pharmacokinetics of insulin uptake by ocular tissues and the role of cerebrospinal fluid in optic nerve insulin accumulation following topical insulin application.

BACKGROUND: As part of our ongoing studies concerning the efficacy of using topically applied medications to treat retinal and optic nerve diseases, we previously showed that insulin accumulated in the retina, optic nerve, and cerebrospinal fluid (CSF) following topical application. The purpose of this study was to investigate which route insulin takes to get to the posterior segment of the eye, and to specifically assess the role of the CSF in optic nerve insulin accumulation. METHODS: Lewis rats that received 125I-insulin eye drops were killed at different time points and their ocular tissues counted in a gamma counter. In order to determine whether elevated levels of CSF insulin could lead to optic nerve insulin accumulation, a separate cohort of animals was injected in their lumbar cistern with unlabeled insulin and their optic nerves later assessed for the presence of insulin by enzyme-linked immunosorbent assay. RESULTS: All ocular tissues (except the lens) showed at least one significant time point elevation in 125I-insulin compared to baseline. Both the combined cornea/iris/ciliary body and the sclera showed a notable, overall increase in counts over baseline, with values at 20 and 30 minutes being significantly elevated. The highest numbers of counts were seen in the aqueous humor. Animals injected intralumbar cisternally with insulin showed elevated insulin concentrations in their optic nerves and cisterna magna-derived CSF that did not appear to be due to uptake of insulin from the circulation. CONCLUSIONS: These results support the hypothesis that the insulin that accumulates in the retina and optic nerve following topical application arrives there after diffusing through the sclera, though an intraocular route--while unlikely--cannot be ruled out.

Administration, Topical↗

Intraocular bacterial contamination during sutureless, small incision, single-port phacoemulsification.

PURPOSE: To evaluate the incidence of anterior chamber bacterial contamination during no-stitch, 1-handed, small incision phacoemulsification. SETTING: Little Company of Mary Hospital, Evergreen Park, Illinois, USA. METHODS: This study comprised 53 eyes of 46 patients. Topical gentamicin sulfate was administered 1 hour preoperatively. After povidone-iodine cleansing solution and povidone-iodine paint (5% and 10%) were applied, the eyes were draped in a sterile manner. Aqueous fluid was aspirated upon entering the anterior chamber and at the end of surgery; the specimens were cultured for up to 14 days. All eyes had no-stitch, 1-handed, small incision phacoemulsification with implantation of a foldable acrylic posterior chamber intraocular lens through a 3.5 mm scleral tunnel incision. RESULTS: Three specimens (5.7%) aspirated on entry into the anterior chamber were positive for microorganisms. Of the cultures obtained at the end of surgery, 4 (7.5%) were positive for microorganisms. All posterior lens capsules were intact. The following organisms were cultured at the end of phacoemulsification: alpha-streptococci, micrococci, saprophytic mold, alpha-viridans streptococci, coagulase-negative Staphylococcus species, and anaerobic positive cocci. No eye developed endophthalmitis. CONCLUSIONS: The incidence of anterior chamber bacterial contamination was low. Bacterial contamination of the anterior chamber occurred at the beginning and toward the end of phacoemulsification. Staphylococcus species was the most common organism in the beginning, while Streptococcus species was the most common at the end. Saprophytic mold was present only at the end. No eye developed endophthalmitis.

Aged↗

The effect of acute experimental retinal vein occlusion on cat retinal vein pressures.

PURPOSE: Retinal ischemic damage associated with retinal vein occlusion is exacerbated by fluid extravasation and hemorrhage, which may be caused by increased permeability, elevated intravascular pressure, or both. Direct measurement of the retinal vein pressure in the cat after acute experimental retinal vein occlusion may define the role of intravascular pressures in fluid extravasation associated with this condition. METHODS: Intravenous retinal pressure measurements were obtained using a micropipette connected to a servonull device and positioned by a robot micromanipulator, while a major retinal vein near the optic disc was occluded by argon laser radiation delivered through an optical fiber positioned by a manual micromanipulator. After occlusion, retinal vein pressures were measured on both sides of the occlusion site at a controlled intraocular pressure of 20 mm Hg. RESULTS: Upstream of the occlusion site, the retinal vein pressures were not greatly elevated, although they were significantly different from controls. Downstream vein pressures were significantly lower than controls, but vascular collapse near the optic nerve was not observed. CONCLUSIONS: In retinal vein occlusion, venous pressures in a segmental retinal circulatory bed are not substantially elevated, thus implying the presence of a pressure-release mechanism and implicating vascular damage for the increased transvascular fluid flux. The lack of vascular collapse downstream of the occlusion site suggests collateral communication before a large intraocular pressure-dependent resistance segment that lies between the intraocular and extraocular vessels.

Acute Disease↗

Carbonic anhydrase inhibitors. Part 60(#). The topical intraocular pressure-lowering properties of metal complexes of a heterocyclic sulfonamide: influence of the metal ion upon biological activity.

Metal complexes of a sulfonamide possessing strong carbonic anhydrase (CA) inhibitory properties have been obtained from the sodium salt of the sulfonamide or from the free sulfonamide in the presence of ammonia, and the following metal ions: Mg(II); Zn(II); Mn(II); Cu(II); Co(II); Ni(II); Be(II); Cd(II); Pb(II); Al(III); Fe(III) and La(III). The original sulfonamide, 5-(3,4-dichlorophenylureido)-1,3,4-thiadiazole-2-sulfonamide and its complexes were assayed for in vitro inhibition of three CA isozymes, CA I, II and IV, some of which play a critical role in ocular fluid secretion. All these compounds (the sulfonamide and its metal complexes) behave as very powerful inhibitors against the three investigated CA isozymes. The parent sulfonamide possesses strong topical pressure lowering effects in rabbits when applied as a 1% solution directly into the eye, but some of its metal complexes, such as the Mg(II); Zn(II); Mn(II) and Cu(II) derivatives, lower intraocular pressure (IOP) in experimental animals much better. Ex vivo data showed a 98.5-99.9% inhibition of CA II and IV in ocular fluids and tissues of the rabbits treated with these agents, proving that the IOP lowering properties are due to CA inhibition. The influence of the different metal ions upon the efficiency of the obtained complexes as pressure lowering drugs are discussed, considering the possibility to design in this way more selective pharmacological agents from this class.

Administration, Topical↗

[Value of studying the intraocular pressure in patients operated on for retinal detachment].

The IOP was checked in 263 eyes operated for retinal detachment--before, during and after surgery. Statistically lower values of the IOP were observed in eyes with retinal detachment in comparison with the healthy fellow-eye and in cases with an extensive and prominent detachment. There was no interdependence between the values of the IOP--even showing considerable oscillations--and the occurrence of complications, the normalization of the postoperative IOP and the results of the treatment. The measurements of the IOP in the course of retinal detachment operation may have a significance in determining the indications for a drainage of the subretinal fluid and in evaluation of the degree of the retinal invagination.

Adolescent↗

NGF treatment promotes development of basal forebrain tissue grafts in the anterior chamber of the eye.

The effects of nerve growth factor (NGF) on developing central cholinergic neurons were studied using intraocular grafts of rat fetal (E17) basal forebrain tissue. Prior to grafting, grafts were incubated in NGF or saline. Transplants were allowed to mature for six weeks, receiving weekly intraocular injections of NGF or saline. Measurements of NGF levels in oculo after one single injection showed that NGF slowly decreases in the anterior chamber fluid, and after one week, low but significant levels were still present in the eye. Following pretreatment with diisopropylfluorophosphate (DFP), the cholinergic neurons in the grafts were analyzed using three morphological markers: antibodies to cholineacetyltransferase (ChAT), antibodies to acetylcholinesterase (AChE Ab) and acetylcholinesterase histochemistry (AChE). The transplants grew well and became vascularized within the first week. The growth of the NGF-treated basal forebrain grafts was significantly enhanced as compared to the growth of the saline-treated grafts evaluated with repeated stereomicroscopical observations directly through the cornea of the ether-anaesthetized hosts. The NGF-treated grafts contained almost twice as many cholinergic neurons seen with all the cholinergic markers used, as the saline-treated grafts. However, there was no difference in cholinergic cell density between the two groups. The morphology and size of an individual cholinergic neuron was similar in the two groups. The fiber density as evaluated with AChE-immunohistochemistry did not change after NGF-treatment. The DFP-treatment did not seem to affect the AChE-immunoreactivity since an extensive fiber network was found, whereas almost no fibers were seen using conventional AChE histochemistry. We have demonstrated that in oculo transplantation of basal forebrain is a useful model for examining in vivo effects of NGF on central cholinergic function. The marked volume increase of NGF-treated grafts and the unchanged density of cholinergic cells and terminals suggests, that NGF increases the survival of not only developing cholinergic neurons, but possibly other non-cholinergic neurons and non-neuronal cells as well. These results support the notion that NGF acts as a neurotrophic factor on cholinergic and possibly non-cholinergic cells in the central nervous system.

Acetylcholinesterase↗

The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.

Our goal is to determine whether adjunctive aqueous suppressants (topical β-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (±timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.

Humans↗

Nitric oxide and vascular endothelial growth factor concentrations are increased but not related in vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: Several reports have implicated nitric oxide (NO) in the angiogenic process. The assessment of NO stable end products, nitrite and nitrate (NOx), is commonly used as a measure of NO production in biological fluids. The aims of the study were to investigate NOx concentrations in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to evaluate the relationship between NOx and vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the time of vitreoretinal surgery from 23 patients with PDR, and 17 control non-diabetic patients with non-proliferative ocular disease. NOx was determined by using the Griess reaction and VEGF levels were assessed by ELISA. RESULTS: The intravitreous concentration of NOx was significantly elevated in patients with PDR in comparison with the control group (31.6 +/- 2.96 micromol/l vs. 18 +/- 2.46 micromol/l; P = 0.01). However, we did not detect any differences between NOx serum concentrations. We observed a correlation between serum and vitreous levels of NOx in diabetic patients (r = 0.79; P < 0.001), but not in the control group. Intravitreous levels of VEGF in patients with PDR were higher than those obtained in serum (1.42 ng/ml (0.12-7.62) vs. 0.12 ng/ml (0.03-0.42); P < 0.01). Vitreal levels of VEGF were strikingly higher in patients with PDR than in the control subjects (1.42 ng/ml (0.12-7.62) vs. 0.009 ng/ml (0.009-0.04); P < 0.001). No correlation between vitreal concentrations of NOx and VEGF was observed, either in diabetic patients or in the control group. CONCLUSIONS: NOx and VEGF are increased but not related in the vitreous fluid of diabetic patients with PDR. Our results suggest that serum diffusion could play a significant role in explaining the increase of NOx. By contrast, intraocular production seems to be the main factor responsible for the intravitreous enhancement of VEGF.

Diabetes Mellitus, Type 1↗

Acute endogenous endophthalmitis due to Bartonella henselae.

A 45-year-old man presented with progressively worsening vitreitis of 1 week's duration. Treatment for cat-scratch disease 3 years prior to presentation and persistent vitreitis led to vitrectomy, and analysis of the vitrectomy specimen revealed inflammatory cells and necrotic debris; polymerase-chain-reaction analysis of the vitreous fluid sample, done by use of a novel heminested protocol, demonstrated the presence of Bartonella henselae DNA. Treatment with doxycycline led to improvement in the intraocular inflammation but resulted in a poor visual outcome.

Acute Disease↗