Structural-visual functional relationships detected by optical coherence tomography in varying age-cohorts' patients with optic neuritis.

AIM: To assess the relationships of final best-corrected visual acuity (BCVA) and the optic nerve structural loss in varying age-cohorts of optic neuritis (ON) patients. METHODS: This is a retrospective, cross-sectional study. Totally 130 ON subjects (200 eyes) without ON onset within 6mo were included, who underwent BCVA assessment, peripapillary retinal nerve fibre layer (pRNFL) and macular segmented layers evaluation by optical coherence tomography (OCT). RESULTS: For the 0-18y cohort, the final BCVA (logMAR) was significantly better and less frequent recurrences than adult cohorts (P=0.000). The final BCVA (logMAR) in all age-cohorts of the ON patients had negative and linear correlations to the pRNFL thicknesses and macular retinal ganglion cell layer (mRGCL) volumes, when the pRNFL thicknesses were reduced to the thresholds of 57.2-67.5 µm or 0.691-0.737 mm3 in mRGCL volumes, respectively, with the strongest interdependence in the 19-40y cohort. The ON patients from varying age cohorts would be threatened by blindness when their pRNFL thicknesses dropped 36.7-48.3 µm or the mRGCL volumes dropped to 0.495-0.613 mm3. CONCLUSION: The paediatric ON has best prognosis and young adult ON exhibits perfectly linear correlations of final vision and structural loss. The pRNFL and the mRGCL could be potential structural markers to predict the vision prognosis for varying-age ON patients.

Structural impairment patterns in peripapillary retinal fiber layer and retinal ganglion cell layer in mitochondrial optic neuropathies.

AIM: To evaluate the structural injure patterns in peripapillary retinal fiber layer (pRNFL), retinal ganglion cell layer (RGCL) and their correlations to visual function in various mitochondrial optic neuropathies (MON) to offer help to their differential diagnosis. METHODS: Totally 32 MON patients (60 eyes) were recruited within 6mo after clinical onsets, including 20 Leber hereditary optic neuropathy (LHON) patients (37 eyes), 12 ethambutol-induced optic neuropathy (EON) patients (23 eyes), and 41 age-gender matched healthy controls (HC, 82 eyes). All subjects had pRNFL and RGCL examinations with optic coherence tomography (OCT) and visual function tests. RESULTS: In the early stages of MON, the temporal pRNFL thickness decreased (66.09±22.57 µm), but increased in other quadrants, compared to HC (76.95±14.81 µm). The other quadrants remaining stable for LHON and EON patients besides the second hour sector of pRNFL thickness reduced and the temporal pRNFL decreased (56.78±15.87 µm) for EON. Total macular thickness in MON reduced remarkably (279.25±18.90 µm; P=0.015), which mainly occurring in the inner circle (3 mm diameter of circle) and the nasal temporal sectors in the outer circle (5.5 mm diameter of circle), in contrast to those in HC. RGCL thickness reduced in each sector of the macula (61.90±8.73 µm; P≤0.001). It strongly showed the correlationship of best corrected visual acuity (R=0.50, P=0.0003) and visual field injury (R=0.54, P=0.0002) in MON patients. CONCLUSION: OCT is a potential tool for detecting structural alterations in the optic nerves of various MON. Different types of MON may have different damage patterns.

Retinal segmented layers with strong aquaporin-4 expression suffered more injuries in neuromyelitis optica spectrum disorders compared with optic neuritis with aquaporin-4 antibody seronegativity detected by optical coherence tomography.

PURPOSE: To evaluate retinal segmented layer alterations in optic neuritis (ON) in an AQP4-Ab seropositive (AQP4-Ab+/ON) cohort and in neuromyelitis optica (NMO) with ON eyes (NMO-ON) compared with an AQP4-Ab seronegative ON (AQP4-Ab-/ON) cohort using optical coherence tomography (OCT). METHODS: We recruited 109 patients with ON (161 eyes) and 47 healthy controls. All patients with ON were subdivided into three subcohorts: 37 patients (54 eyes) with AQP4-Ab+/ON, 45 patients (65 eyes) with AQP4-Ab-/ON and 27 patients (42 eyes) with NMO-ON. All subjects were evaluated for their peripapillary retinal nerve fibre layer (pRNFL) and inner macular segmented layer using OCT. RESULTS: AQP4-Ab+/patients with ON had the same structural injury patterns as patients with NMO-ON, and the injury patterns were distinct from those of AQP4-Ab-/patients with ON. NMO-ON and AQP4-Ab+/ON preferentially damaged the pRNFL (all p=0.000), the macular retinal nerve fibre layer (mRNFL; p=0.000 and 0.032, respectively), and the inner plexiform layer (IPL; p=0.000 and 0.006, respectively) without differences in the retinal ganglion cell layer (p=0.106 and 0.374, respectively) compared with AQP4-Ab-/patients with ON. The thickness of the inner nuclear layer (INL) increased in NMO-ON (p=0.043) compared with that of AQP4-Ab-/ON without a significant difference in AQP4-Ab+/ON versus AQP4-Ab-/ON (p=0.353). When the thickness of the inferior nasal quadrant (NI) of the pRNFL was reduced to ≤46.5 µm (area under the curve 0.772, sensitivity 89.2% and specificity 57.5%) 6 months after ON onset, NMO was considered. CONCLUSIONS: AQP4-Ab+/ON produced similar structural injury patterns as NMO-ON. The pRNFL, mRNFL and IPL in the two types of ON and the INL in NMO-ON suffered more damage than those in AQP4-Ab-/ON, which could be associated with strong aquaporin-4 expression. The thickness of the NI of the pRNFL could be a potential clue for predicting ON progression to definite NMO.

Macular thickness as a predictor of loss of visual sensitivity in ethambutol-induced optic neuropathy.

Ethambutol is a common cause of drug-related optic neuropathy. Prediction of the onset of ethambutol-induced optic neuropathy and consequent drug withdrawal may be an effective method to stop visual loss. Previous studies have shown that structural injury to the optic nerve occurred earlier than the damage to visual function. Therefore, we decided to detect structural biomarkers marking visual field loss in early stage ethambutol-induced optic neuropathy. The thickness of peripapillary retinal nerve fiber layer, macular thickness and visual sensitivity loss would be observed in 11 ethambutol-induced optic neuropathy patients (22 eyes) using optical coherence tomography. Twenty-four healthy age- and sex-matched participants (48 eyes) were used as controls. Results demonstrated that the temporal peripapillary retinal nerve fiber layer thickness and average macular thickness were thinner in patients with ethambutol-induced optic neuropathy compared with healthy controls. The average macular thickness was strongly positively correlated with central visual sensitivity loss (r (2) =0.878, P=0.000). These findings suggest that optical coherence tomography can be used to efficiently screen patients. Macular thickness loss could be a potential factor for predicting the onset of ethambutol-induced optic neuropathy.

Effect of brain-derived neurotrophic factor on c-jun expression in the rd mouse retina.

AIM: To determine the location of c-jun protein, dynamic changes in c-jun mRNA and protein expression, and ultrastructure characteristics in the rd mouse retina, following a single dose of brain-derived neurotrophic factor (BDNF) in a short period of time. METHODS: A single intravitreal injection of BDNF at two dosages (25µg/L or 50µg/L) was given to the right eye of the rd mouse at age 2 and 3 weeks respectively. Two weeks after injection, the location of c-jun protein in the retina was observed by immunofluorescence detection, c-jun mRNA and protein expression in retinas were detected by quantitative real time polymerase chain reaction (RT-PCR) and western immunoblotting analysis, ultrastructure characteristics of retinas were detected by transmission electron microscope (TEM) observation. RESULTS: c-jun protein was expressed in the inner nuclear layer (INL) of retina. BDNF at two dosages (25µg/L and 50µg/L) increased c-jun mRNA expression at PN-4 weeks respectively (P(1)=0.019, P(2)=0.021). 50µg/L BDNF increased c-jun protein expression at PN-4 weeks (P =0.000). The retinal ultrastructure was improved. CONCLUSION: The effects of BDNF exerts on the c-jun expression in the retina are dose-dependent and time-dependent, which may mediate photoreceptor rescue indirectly in the pathological process of retinitis pigmentosa (RP) at early stage.

[Current opinions about using of medication intervention as neuroprotective therapy for degenerative ocular fundus diseases].

Recently, many studies indicated that certain medications can delay the apoptosis of retinal nerve cells at different points during the process of apoptosis and have neuroprotective effect on preventing degenerative ocular fundus diseases. N-methyl-D-aspartate receptor (NMDAR) antagonists, NMDAR-associated calcium channel blockers and acetylcholine receptor agonists have been shown to have neuroprotective effects for retinal damages by inhibiting NMDA-induced excitotoxicity. The inhibitors of nitric oxide synthase (NOS) can prevent the cell apoptosis and reduce the retinal cell loss by suppressing the activity of NOS as well as the production of the nitric oxide. Antioxidants and some Chinese traditional medicine with antioxidant activities can also have protective effect on retinal damage caused by degenerative ocular fundus diseases through their functions in decreasing the peroxidation reaction and the production of the superoxide radicals in the cells. In addition, activation of neurotrophic factor receptors by their ligands plays a key role in neuroprotective and trophic effects for the retina. All of these studies not only provide the foundation, but also offer new theoretical supports for drug neuroprotective therapies in clinical practice.

[Studies of the physiological function of carbonic anhydrase].

Carbonic anhydrases (CA) is a zinc-enzyme family. They are involved in multiple aspects of systemic and cellular acid-base balance. This review is a general introduction to the disposition, molecular constitution,biological function and physiological function of CA.