Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi, and animals. Several studies have indicated that melatonin synthesis occurs in the retina of most vertebrates, including mammals. The retinal biosynthesis of melatonin and the mechanisms involved in the regulation of this process have been extensively studied. Circadian clocks located in the photoreceptors and retinal neurons regulate melatonin synthesis in the eye. Photoreceptors, dopaminergic amacrine neurons, and horizontal cells of the retina, corneal epithelium, stroma endothelium, and the sclera all have melatonin receptors, indicating a widespread ocular function for melatonin. In addition, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect that it exerts even during ischemia. Melatonin cytoprotective properties may have practical implications in the treatment of ocular diseases, like glaucoma and age-related macular degeneration.

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8–9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.

Primary open angle glaucoma (POAG) is a leading cause of late onset, progressive, irreversible blindness and, although its etiology is poorly understood, elevated intraocular pressure (IOP) often appears to be a contributory factor. Proteomic and Western analyses of trabecular meshwork (TM) from patients with POAG and age-matched controls originally implicated cochlin as possibly contributing to glaucoma pathogenesis. Cochlin deposits were subsequently detected in glaucomatous but not in control TM and older glaucomatous TM was found to contain higher levels of cochlin and significantly lower amounts of collagen type II. More recently, similar results were reported in DBA/2J mice, which at older ages develop elevated IOP, retinal ganglion cell degeneration, and optic nerve damage. Notably, cochlin was absent in TM from C57BL/6J, CD1, and BALBc/ByJ mice, which do not exhibit elevated IOP or glaucoma. Cochlin was found in the TM of very young DBA/2J mice, prior to elevated IOP, suggesting that over time the protein may contribute to the events leading to increased IOP and optic nerve damage. Here we review these findings and describe how future studies in DBA/2J mice can help resolve whether cochlin plays a causal role in mechanisms of POAG and elevated IOP.

Summary

Background and aim: Rocuronium may be given to patients for intubation and also after they have received suxamethonium for intubation. The neuromuscular profile of rocuronium given after recovery from suxamethonium may not be identical to that when rocuronium has been given alone. The neuromuscular effects of suxamethonium and rocuronium, and their effects on intraocular pressure (IOP), heart rate (HR) and arterial pressure were also recorded.

Methods: Thirty patients were randomly allocated to receive either 0.6 mg kg−1 rocuronium (n = 15) or 1 mg kg−1 suxamethonium (n = 15) for intubation. Anaesthesia was first induced using propofol 2.5 mg kg−1 and fentanyl 2 μg kg−1 and maintained with propofol 6–12 mg kg−1h−1. The response of the thumb to supramaximal train-of-four (TOF) ulnar nerve stimulation at the wrist was measured using a mechanomyograph. In the suxamethonium group, when the first twitch of the TOF had recovered to 90%, rocuronium 0.6 mg kg−1 was administered. Before administration of relaxant, baseline readings of HR, arterial pressure and IOP were measured until stable, then the appropriate relaxant administered. Thereafter, all readings were repeated at 30, 90, 150, 210 and 270 s. Tracheal intubation was performed 300 s after the intubating dose and all recordings repeated 30 s later. Mechanomyographic monitoring was continued until 70% TOF recovery.

Results: Suxamethonium had a more rapid onset than rocuronium (49 s vs. 74 s, P < 0.0001). The onset time of rocuronium after suxamethonium was significantly reduced (56 s) and the time to recover to a TOF of 70% following rocuronium was increased by previous suxamethonium administration (47 vs. 58 min, P < 0.05). Suxamethonium caused a marked rise in IOP (>30%) and HR (>10%) while rocuronium had little effect on either.

Conclusion: Previous suxamethonium administration decreases the onset time and increases the duration of action of rocuronium. Unlike suxamethonium, rocuronium has few cardiovascular effects and causes little change in IOP.

Most primate retinas have an area dedicated for high visual acuity called the fovea centralis. Little is known about specific mechanisms that drive development of this complex central retinal specialization. The primate area of high acuity (AHA) is characterized by the presence of a pit that displaces the inner retinal layers. Virtual engineering models were analyzed with finite element analysis (FEA) to identify mechanical mechanisms potentially critical for pit formation. Our hypothesis is that the pit emerges within the AHA because it contains an avascular zone (AZ). The absence of blood vessels makes the tissue within the AZ more elastic and malleable than the surrounding vascularized retina. Models evaluated the contribution to pit formation of varying elasticity ratios between the AZ and surrounding retina, AZ shape, and width. The separate and interactive effects of two mechanical variables, intraocular pressure (IOP) and ocular growth-induced retinal stretch, on pit formation were also evaluated. Either stretch or IOP alone produced a pit when applied to a FEA model having a highly elastic AZ surrounded by a less elastic region. Pit depth and width increased when the elasticity ratio increased, but a pit could not be generated in models lacking differential elasticity. IOP alone produced a deeper pit than did stretch alone and the deepest pit resulted from the combined effects of IOP and stretch. These models predict that the pit in the AHA is formed because an absence of vasculature makes the inner retinal tissue of the AZ very deformable. Once a differential elasticity gradient is established, pit formation can be driven by either IOP or ocular growth-induced retinal stretch.

Background and objective: The aim was to determine if the intravenous administration of sufentanil or clonidine before the induction of anaesthesia could obtund the increase of intraocular pressure associated with rapid-sequence induction.

Methods: Thirty-two ASA I—II patients with no history of eye illness scheduled for elective non-ophthalmic surgery were randomly assigned to receive either sufentanil 0.05 µg kg−1 i.v. (Group A, n = 15) or clonidine 2 µg kg−1 i.v. (Group B, n = 17) prior to induction. General anaesthesia was induced with thiopental (5 mg kg−1) followed by succinylcholine 1 mg kg−1 to facilitate tracheal intubation. The general anaesthetic technique was standardized in both groups. Intraocular pressure was measured using the Schioetz tonometer just before the succinylcholine administration (t0), just before tracheal intubation (t1) and immediately after intubation (t2). Mean arterial pressure and heart rate were recorded at the same time intervals.

Results: Intraocular pressures were similar in both groups at t0, but the sufentanil group had significantly lower values compared with the clonidine group just before (t1) and immediately after tracheal intubation (t2).

Conclusions: Sufentanil is effective in blunting the increase in intraocular pressure caused by rapid-sequence induction with succinylcholine, while clonidine did not seem to have any effect in intraocular pressures just before (t1) and just after (t2) intubation.

Background and objective: The aim was to examine the course of intraocular pressure after relaxation with different doses of cisatracurium.

Methods: The investigation was carried out as a prospective, randomized double-blind study in a crossover design in 30 postoperative patients with stable haemodynamic and respiratory function (ASA I and II). To exclude any disrupting factors, patients remained intubated and continuously sedated. Twenty patients received an intubation dose (2 × ED95) of cisatracurium (0.1 mg kg−1) compared with atracurium (0.5 mg kg−1). In a second series, 10 patients were given an effective dose, ED95 (0.05 mg kg−1), and a repeat dose (0.02 mg kg−1) of cisatracurium. The intraocular pressure was determined before (T0) as well as 1 (T1), 5 (T5), 10 (T10), 15 (T15), 20 (T20) and 45 (T45) min after bolus administration.

Results: Intraocular pressure decreased after an intubation dose of either cisatracurium or atracurium, and reached a minimum after 10 min (6.7 ± 2.2 and 7.9 ± 2.1 mmHg, respectively). There was no significant difference between either muscle relaxant (P = 0.27). When lower doses of cisatracurium (0.05 and 0.02 mg kg−1) were applied, the intraocular pressure also decreased, albeit to a lesser extent and with a delayed onset (8.4 ± 1.9 mmHg after 10 min, 9.9 ± 3.4 mmHg after 15 min). There was no significant difference between dosages (P = 0.44).

Conclusions: Cisatracurium is a useful drug in patients when a decrease of intraocular pressure is wanted and where muscle relaxation is necessary and acceptable.

Patients with bilateral corneal blindness in whom corneal transplantation has either been unsuccessful or inappropriate may be considered for osteo–odontokeratoprosthesis surgery. During a two–stage procedure the surface of the cornea is removed and covered with a graft of buccal mucosa. An optical cylinder, supported by an osteo–odonto lamina planed from a tooth is then inserted into the mucosa to act as a lens. The anaesthetic implications of this operation include care of patients from a wide age range, often with underlying medical problems undergoing two operations of prolonged duration. The eye can be ‘open’ during both stages of the operation and anaesthetic techniques directed towards prevention of rises in vitreal pressure are essential. This article outlines the surgical process of osteo-odonto-keratoprosthesis surgery with reference to our anaesthetic experiences from nine cases.