Systemic anti-cancer treatment has evolved rapidly with the introduction of immunotherapy and targeted therapies, substantially improving survival across a broad spectrum of malignancies. However, as their use expands, ophthalmic toxicities are increasingly recognised as clinically significant adverse effects. This review outlines the pathophysiology, clinical spectrum and management strategies for ophthalmic adverse events linked to immune checkpoint inhibitors, MEK, BRAF, FGFR, ERK, EGFR, HER2, BTK, FLT-3, Bcr-Abl, ALK inhibitors and antibody-drug conjugates.
Intraocular inflammation (IOI) is a rare but potentially sight-threatening complication that can occur after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. This adverse event has been under scrutiny in recent years due to an increased incidence, particularly with some of the newer anti-VEGF agents, such as Brolucizumab. Faricimab is a new anti-VEGF medication that has been approved by the United States Food and Drug Administration. As it is relatively new on the market, long-term safety data is still being collected. This is a retrospective case series of 8 eyes in 5 patients with IOI that occurred after faricimab intravitreal injections. All patients were diagnosed with significant uveitis with anterior vitreous involvement and 4 out of the 5 patients presented subacutely with high intraocular pressure while the remaining patient presented acutely within 4 days following IVT with normal intraocular pressure. The patients received, on average, 4.875 faricimab injections prior to development of IOI and the inflammation resolved in all patients following cessation of faricimab injections and initiation of oral and topical non-steroidal anti-inflammatory agents and topical steroids. Non-infectious hypertensive uveitis can occur subacutely after intravitreal faricimab injections. It is imperative that intraocular pressure is promptly managed to reduce the risk of permanent glaucomatous damage. As all our patients presented with anterior vitreous involvement, it is also practical that such cases of IOI are not mistaken for infectious exogenous endophthalmitis to avoid unnecessary treatment with intravitreal antibiotics and surgery.
Intraocular lymphomas, including vitreoretinal and choroidal lymphoma, can simulate the clinical presentation of other benign and malignant ocular diseases resulting in diagnostic delays. Multimodal imaging features can raise early clinical suspicion to support appropriate subspecialty referrals and treatment for patients affected by these conditions. This review synthesises current evidence on the diagnostic and prognostic value of characteristic imaging features of these rare malignancies. Findings are reviewed based on imaging modality, including fundus photography, optical coherence tomography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, and ultrasound. We emphasise discriminative biomarkers that heighten suspicion for either vitreoretinal or choroidal lymphoma, as well as key findings to discriminate between lymphoma and alternative diagnoses. We further describe longitudinal changes in multimodal imaging features that can facilitate tracking disease progression or treatment response. By consolidating modality-specific findings, this review aims to facilitate early referral and accurate diagnosis of these rare malignancies.
Optical coherence tomography angiography is a burgeoning imaging modality in Ophthalmology. In this review, we outline the breadth of potential utility for optical coherence tomography angiography for diagnosis and prognostication in neuro-ophthalmology. Further mapping of the characteristics and natural history of the optic disc vascular network in neuro-ophthalmic conditions is necessary to increase the utility of this imaging modality for neuro-ophthalmic conditions, as the specificity and sensitivity of optical coherence tomography angiography are currently limited by the small pool of available observational data.
Strabismus is a feature of many genetic syndromes, with highly variable penetrance. The congenital cranial dysinnervation disorders (CCDDs) result in paralytic strabismus, with limited eye movements. CCDDs result from either deficits in differentiation of the cranial motor neuron precursors or from abnormal axon guidance of the cranial nerves. Although most individuals with comitant strabismus are otherwise healthy, strabismus is a variable feature of many genetic syndromes, most commonly those associated with intellectual disability. We review 255 genetic syndromes in which strabismus has been described and discuss the variable penetrance. The association with intellectual disability and neurological disorders underscores the likely neurological basis of strabismus, but the variable penetrance emphasises the complexity of strabismus pathophysiology. The syndromes described here mostly result from loss of function or change in function of the responsible genes; one hypothesis is that nonsyndromic strabismus may result from altered expression or regulation of the same genes.
Optical coherence tomography (OCT) is an in vivo imaging modality that provides non-invasive, high resolution and fast cross-sectional images of the optic nerve head, retina and choroid. OCT angiography (OCTA) is an emerging tool. It is a non-invasive, dye-free imaging approach of visualising the microvasculature of the retina and choroid by employing motion contrast imaging for blood flow detection and is gradually receiving attention for its potential roles in various neuro-ophthalmic and retinal conditions. We will review the clinical utility of the OCT in the management of various common neuro-ophthalmic and neurological disorders. We also review some of the OCTA research findings in these conditions. Finally, we will discuss the limitations of OCT as well as introduce other emerging technologies.
We aimed to describe a 2-year outcome of eyes managed by practitioners benchmarked using a funnel plot by their frequency of treatment using vascular endothelial growth factor (VEGF) inhibitors for naive retinal vein occlusion (RVO). A multicentre, international, observational study of 29 doctors in 12 countries managing 1110 eyes with RVO commencing VEGF inhibitors between 1 January 2012–2022 tracked in the Fight Retinal Blindness! registry. We identified 3 outlying ‘intensive’ practitioners (managing 350/1110 eyes [32%]), 22 ‘typical’ practitioners (604/1110, [54%]) and 4 outlying ‘relaxed’ practitioners (156/1110, [14%]) with respective 24-month outcomes in Branch and Central RVO including the primary outcome, mean adjusted change in visual acuity (VA) in BRVO: +16.2, +13.6, +9.3 letters ( p < 0.01) and CRVO: +14.2, +12.7, +4.8 letters ( p < 0.01); adjusted change in macular thickness in BRVO −179, −150, −159 μm ( p < 0.01) and CRVO −324, −283, −232 μm ( p < 0.01); time-in-range with VA > 68 letters in BRVO 90, 78, 68 weeks ( p < 0.01) and CRVO 69, 60, 54 weeks ( p = 0.04); median injections 18, 13 and 10; median final injection intervals, BRVO 6, 9, 10 weeks and CRVO 6, 9 and 12 weeks; with no significant difference in adverse outcomes. At 24 months, the intensive practitioners were treating RVO using VEGF inhibitors with twice the frequency of the relaxed practitioners; however, their patients had gained twice (BRVO) to three times (CRVO) more letters of VA.
To investigate visual cognitive functions, including visual attention, executive function, and visual working memory, in children with anisometropic amblyopia versus those with normal vision. Thirty-five children with anisometropic amblyopia and 34 with normal vision participated. Visual acuity, stereoacuity, and contrast sensitivity were measured, followed by the Cambridge Neuropsychological Test Automated Battery's six subtests for cognitive evaluation. Visual attention was assessed using reaction time (RTI) and rapid visual information processing (RVP). Executive function was evaluated through the multitasking test (MTT). Visual working memory was assessed with spatial working memory (SWM), delayed matching to sample (DMS), and paired association learning (PAL), all under binocular conditions. The amblyopia group exhibited longer reaction and movement times in the RTI than the control group ( p < 0.01). A trend towards lower RVP A' scores, reflecting reduced ability to detect target sequences, appeared in the amblyopia group ( p = 0.056). Amblyopic children demonstrated a lower multitasking cost in the MTT compared with the control group ( p = 0.04). As difficulty increased in the SWM (from four to six boxes), amblyopic children revisited more ( p = 0.01). In the DMS task, while no differences were observed across all delay times ( p = 0.55), amblyopic children performed significantly worse than the control group under the 12-second delay ( p = 0.04). In the eight-pattern PAL condition, the amblyopia group made more errors ( p = 0.01). Children with anisometropic amblyopia performed poorly on neuropsychological tests, particularly visual attention and working memory, but outperformed the control group in multitasking. These findings highlight the broader cognitive impacts of anisometropic amblyopia beyond vision.
To evaluate the clinical presentation, pathological features and outcomes of retinoblastoma based on the race of origin in a global cohort of patients. Retrospective collaborative study of 1426 patients who underwent primary enucleation for retinoblastoma. Patients were grouped into Caucasians ( n = 231, 16%), Asians ( n = 841, 59%), Hispanics ( n = 226, 16%), Arabs ( n = 96, 7%) and Others (Africans, African Americans, Indigenous Australians; n = 32, 2%) cohorts. On histopathology, massive choroidal invasion was higher in Asians (30%) and Hispanics (26%) than Caucasians (15%, p < 0.001). Post-laminar optic nerve invasion was higher in Asians (28%), Hispanics (20%) and Others (9%) than Caucasians (11%, p < 0.001). At a mean follow-up of 41 months (median, 35 months; range, < 1–149 months), tumour recurrence and metastasis-related death was higher in Hispanics (9% and 12%, respectively), Asians (4% and 13%, respectively) and Others (6% and 6%, respectively). Multivariate Cox proportional hazards analysis of outcomes based on race with 8th edition AJCC pT stage and adjuvant therapy as covariates revealed 6.8 times greater risk for orbital tumour recurrence in Hispanics compared to Caucasians ( p = 0.010) and 3.2 times risk hazards for metastasis-related death in Hispanics and Asians compared to Caucasians ( p = 0.028 and p = 0.038, respectively). The histopathological features in primarily enucleated eyes with retinoblastoma vary with race. Despite adjusting for tumour staging and adjuvant treatment, race remains an independent predictor of outcomes, including orbital tumour recurrence and metastasis-related death. A stringent follow-up and a more aggressive treatment approach is recommended in Asians and Hispanics who manifest high-risk histopathological features.
To evaluate the 6-year physiological rates-of-change in ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thickness measured with optical coherence tomography. We included 2202 out of 2661 subjects from the population-based Singapore Chinese Eye Study who returned for follow-up 6 years after baseline examination (follow-up rate 87.7%). OCT scans with signal strength (SS) <6, imaging errors, and ocular pathologies were excluded. A linear mixed model was used to measure the rates-of-change in GCIPL and RNFL thickness. Time and difference between baseline and follow-up scan SS were modelled as fixed effect. Baseline age, baseline measurement, gender, hypertensive medication, diabetes status, cardiovascular disease, smoking status, body mass index, spherical equivalent (SE), intraocular pressure and optic disc area were each analysed in an interaction term with time. The adjusted mean rate-of-change in average GCIPL was −0.312 μm/year in males and −0.235 μm/year in females. Older age and thicker GCIPL thickness at baseline were associated with higher rates-of-change while females and more hyperopic SE were associated with lower rates-of-change. The adjusted mean rate-of-change in average RNFL was −0.374 μm, with higher rates-of-change in the vertical quadrants and no differences between genders. Older age and thicker RNFL thickness at baseline were associated with higher rates-of-change in average RNFL and RNFL thickness in the vertical quadrants, and vice versa for each unit increase in scan SS and SE. Our population cohort provides data on physiological thinning of GCIPL and RNFL with age. Differentiating physiological changes in GCIPL and RNFL is important for more accurate clinical assessment.
Improved vision self-monitoring tools are required for people at risk of neovascular complications from age related macular degeneration (AMD). to report the self-monitoring habits of participants with intermediate AMD using the Amsler grid chart, and the use of personal electronic devices and gameplay in this over 50 year old cohort. single-centre descriptive study carried out at the Centre for Eye Research (CERA), Melbourne, Australia. 140 participants over 50 years of age, with a diagnosis of intermediate AMD and best-corrected visual acuity (BCVA) of ≥6/12 in each eye. structured questionnaire survey of participants who were enrolled in natural history of AMD studies at CERA. frequency of vision self-monitoring using the Amsler grid chart, and frequency of general use of personal electronic devices and gameplay. Of 140 participants with mean age of 70.5 years, 83.6% used an Amsler grid chart, but only 39.3% used it once per week. Most participants (91.4%) used one or more personal electronic devices. Of these, over half (54.7%) played games on them, among whom 39% played games once a day. Of participants aged 50–69 years, 92% (95%CI 85.1–98.9) were willing to play a game to monitor their vision, compared to 78% (95%CI 69.0–87.0) of those aged 70 years and older ( P < 0.05). a large proportion of AMD patients already use personal electronic devices. Gamification techniques are likely to increase compliance with self-monitoring, leading to earlier detection in the next generation of patients with neovascular AMD.
