VOLUME 85 - ISSUE 1

PURPOSE: To examine subbasal corneal nerve changes in patients with bacterial infectious keratitis using in vivo confocal microscopy.
METHODS: Thirteen patients (13 eyes) with unilateral bacterial keratitis and 12 healthy controls were prospectively enrolled in the study. In vivo confocal microscopy was performed in all the patients at 2 time points, in the acute phase of infectious keratitis and at 28 ± 0.6 months after resolution of the infection.
RESULTS: The subbasal nerve length was 5.15 ± 1.03 mm/mm² during the acute phase of bacterial keratitis (compared with that of the controls: 19.02 ± 1.78 mm/mm², p<0.05). Despite the significant corneal nerve regeneration over the interval of 28 months after the resolution of the infection, the nerve density was still significantly reduced as compared with that of the controls (9.73 ± 0.93 mm/mm², p<0.05). Moreover, in vivo confocal microscopy images showed diffuse high-reflecting areas referring to the scar tissue areas with thin and tortuous nerve branches regenerating toward these areas.
CONCLUSIONS: A partial corneal nerve regeneration of subbasal nerve plexus during the first 28 months after the acute phase of infectious keratitis was observed. Moreover, the regenerated nerves of the patients remained morphologically altered as compared with those of the healthy controls. These results may be relevant to the clinical follow-up and surgical planning for these patients.

Keywords: Cornea/innervation; Ophthalmic nerve; Eye infections, viral; Keratitis, herpetic; Microscopy, confocal

Purpose: Age-related macular degeneration is the most common cause of blindness in developed countries, and several factors have been attributed for its etiology. This study was conducted to explore the relationship between serum vitamin D levels and age-related macular degeneration.
Methods: We retrospectively analyzed the data of 114 patients with age-related macular degeneration. A total of 102 patients who did not have any other diseases than refractive error were allocated to the control group. The best-corrected visual acuity, fundus findings, and spectral domain optical coherence tomography findings were analyzed. Patients were allocated to groups based on the Age-related Eye Disease Study classification. Serum 25(OH) vitamin D levels were measured. The central foveal thickness and the subfoveal choroidal thickness were measured by optical coherence tomography.
Results: The 25(OH) vitamin D levels in age- and gender-matched patients with age-related macular degeneration and in healthy subjects were 14.6 ± 9.8 and 29.14 ± 15.1 ng/ml, respectively. The age-related macular degeneration group had significantly lower vitamin D levels than the control group (p>0.001). The subfoveal choroidal thickness was lower in patients with age-related macular degeneration (p>0.001). The 25(OH) vitamin D level showed a weak positive correlation with choroidal thickness (r=0.357, p=0.01). When the level of 25(OH) vitamin D was evaluated according to the stages of age-related macular degeneration, it was found to be lower in the advanced-stage disease (p=0.01). The risk for the development of choroid neovascular membrane and subretinal fibrosis was found to increase with decreased vitamin D levels.
Conclusions: Significantly decreased levels of 25(OH) vitamin D in advanced-stage age-related macular degeneration suggest a significant correlation existing between vitamin D deficiency and age-related macular degeneration development. Further studies are required to examine whether vitamin D supplementation has an effect on the development and progression of age-related macular degeneration.

Keywords: Choroid neovascular membrane; Macular degeneration; Optical coherence Tomography; Fibrosis; Retina; Vitamin D; Vitamin D deficiency

Purpose: To collect data on the rate and efficacy of tobacco counseling sessions delivered by ophthalmologists under the setting of patients with thyroid eye disease.
Methods: We analyzed the electronic medical records of a digital cohort of patients who visited ophthalmologists at the University of Pennsylvania Health System from 2012 to 2017 with reference to the International Classification of Disease (ICD) codes for Graves’ disease, thyrotoxic exophthalmos, and/or thyroid eye disease. Tobacco histories were recorded at the first and last ophthalmology office visits or the most temporally proximal encounter in packs/day (ppd), and each ophthalmology visit note was analyzed to validate the occurrence of tobacco counseling.
Results: A total of 435 patients met our study inclusion criteria, of which 72 (16.6%) were active smokers at the time of their first visit. Only 57 (79.2%) of these active smokers had recorded smoking burdens, 34 (59.6%) of which received at least one form of recorded tobacco counseling session. Nine (26.5%) of the subjects who received tobacco counseling and 1 (4.3%) of those who did not have a recorded counseling, quit smoking (risk difference of 22.1%; 95% CI, [1.7%, 39.1%]; p=0.04). In addition, 17 (50.0%) of the subjects who received counseling and 7 (30.4%) of those who did not have a recorded counseling, reduced their ppd consumption (risk difference of 19.6%; 95% CI [-6.3%, 41.3%]; p=0.18). Overall, 14 (25.5%) out of the 55 ophthalmologists who were active smokers had recorded evidence of tobacco counseling.
Conclusions: Our cumulative results provide the consequence of both missed opportunities for tobacco counseling as well as its efficacy in the setting of thyroid eye disease.

Keywords: Tobacco use; Counseling; Thyroid diseases; Eye diseases; Graves’ disease; Eye diseases

Purpose: The aim of this study was to compare the effects of topical cyclosporine 0.1% and bevacizumab on experimentally induced corneal neovascularization in a rat model.
Methods: A total of 30 adult Sprague-Dawley rats were used in this experimental study. The central cornea of the rats was cauterized chemically. The rats were randomly enrolled into three groups as follows: Group 1 received bevacizumab 1%, Group 2 received cyclosporine 0.1%, and Group 3 received isotonic saline twice a day for 28 days. Slit-lamp examination of all rats was performed at the 3rd and 28th day. The rats were then sacrificed, and the corneas were excised. The number of blood vessels, state of inflammation, and collagen formation were evaluated histopathologically in the corneal sections.
Results: Corneal opacity and edema grades were significantly lower in Group 2 than in Group 3 (p=0.04 and 0.00, respectively). In the histopathological examination, Group 2 demonstrated significantly lesser number of blood vessels than Group 3 (p=0.001). Regarding collagen formation, Group 2 exhibited more regular collagen formation than Groups 1 and 3 (p=0.03). Inflammation grades were significantly lower in Groups 1 and 2 than in Group 3 (p=0.014 and 0.001, respectively).
Conclusion: Topical bevacizumab is effective in inhibiting newly formed corneal neovascularization. The topical cyclosporine 0.1% treatment appears to be more effective than the topical bevacizumab treatment.

Keywords: Corneal neovascularization; Bevacizumab; Cyclosporine A; Rats

Purpose: To evaluate and compare variations in pupillary diameter before and after cataract surgery by conventional phacoemulsification versus femtosecond laser assisted cataract surgery, using LDV Z8 (Ziemer Ophthalmic). We also evaluated the relationship between pupillary diameter and surgery time and ultrasound time.
Methods: Prospective comparative study, carried out at the Center of Excellence in Ophthalmology, Brazil. We included 79 eyes of 67 patients with nuclear opacity. The patients were divided into the control and study groups, including those who underwent cataract surgery with manual phacoemulsification, and femtosecond laser assisted cataract surgery, respectively. All surgeries were performed by the same experienced surgeon. All patients received topical non-steroidal anti-inflammatory drugs on the day before surgery and the same mydriatic eye drops preoperatively. To quantify pupillary size, measurements were performed using a surgical compass: anterior to the phacoemulsification procedure and at the end of the surgery. In the study group, measurements after laser were added. Surgical time and phacoemulsification time were also analyzed.
Results: No significant difference was found between the pre-femto × pre-phaco pupil size (8.69 ± 0.44 mm × 8.63 ± 0.72 mm; p=0.643), and the pupil size at the end of surgery (7.96 ± 0.98 mm × 7.78 ± 0.95 mm; p=0.480) and the mean time of surgery (p=0.780). However, in the femtosecond laser assisted cataract surgery group, a transient increase in pupillary diameter after laser treatment was observed, indicating a tendency for greater variation in the femto group.
Conclusions: Although pupil size diameter was similar at the end of surgery, the femtosecond laser assisted cataract surgery group presented higher intraoperative pupil variation. The surgeon should be aware of pupil size diameter before surgery for better and safer performance of femtosecond laser assisted cataract surgery.

Keywords: Cataract; Miosis; Phacoemulsification; Laser; Pupil

Purpose: Numerous neuroimaging and ophthalmic studies suggest optic nerve involvement in fibromyalgia syndrome. To further elucidate the etiopathogenesis of fibromyalgia syndrome, we compared optic nerve head blood flow area and retinal nerve fiber layer thickness between patients and controls and investigated the associations of these measures with fibromyalgia syndrome severity.
Methods: Participants were divided into the following three groups according to Fibromyalgia Impact Questionnaire score: mild-moderate fibromyalgia syndrome (Group 1, n=47), severe fibromyalgia syndrome (Group 2, n=38), and healthy controls (Group 3, n=38). The optic nerve head blood flow area and retinal nerve fiber layer thickness were measured by optical coherence tomography angiography and compared among groups by ANOVA. Associations with fibromyalgia syndrome severity were evaluated by Spearman’s correlation analysis.
Results: Optic nerve head blood flow area did not differ between fibromyalgia syndrome Groups 1 and 2 (1.61 ± 0.08 vs.1.63 ± 0.09 mm²), but it was significantly lower in control Group 3 (1.49 ± 0.10 mm², all p=0.001). Average retinal nerve fiber layer thickness values were significantly lower in Group 2 (101.18 ± 6.03 µm) than in Group 1 (103.21 ± 10.66 µm) and Group 3 (106.51 ± 8.88 µm) (p=0.041 and 0.020, respectively). The inferotemporal (134.36 ± 12.19 µm) and inferonasal (109.47 ± 16.03 µm) quadrant retinal nerve fiber layer thickness values were significantly lower in Group 2 than in Group 1 [inferotemporal (142.15 ± 17.79 µm), inferonasal (117.94 ± 20.53 µm)] and Group 3 [inferotemporal (144.70 ± 16.25 µm), inferonasal (118.63 ± 19.01 µm)] [inferotemporal, p=0.017 and 0.010, respectively; inferonasal, p=0.047 and 0.045, respectively]. The nasal-superior quadrant retinal nerve fiber layer thickness value was higher in Group 3 (91.08 ± 12.11 µm) than in Group 1 (84.34 ± 13.09 µm) and Group 2 (85.26 ± 13.11 µm) (p=0.031 and 0.038, respectively). A weak correlation was detected between disease severity and optic nerve head blood flow area.
Conclusion: Neural and vascular structures of the eye are altered in fibromyalgia syndrome, particularly among severe cases. Therefore, optical coherence tomography angiography may provide valuable information for the diagnosis and elucidation of fibromyalgia syndrome pathophysiology.

Keywords: Fibromyalgia; Tomography, optical coherence; Angiography; Optic nerve/blood supply; Nerve fibers; Retina

Purpose: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone.
Methods: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m²) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months.
Results: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group.
Conclusions: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.

Keywords: Diabetic retinopathy; Light coagulation; Ranibizumab; Bevacizumab; Contrast sensitivity; Vascular endothelial growth factor A; Intravitreal injection

Purpose: The high prevalence and severity of congenital toxoplasmosis in Brazil, with several affected individuals progressing to low vision, emphasize the importance of evaluating their quality of life. In this study, the Children’s Visual Function Questionnaire (CVFQ) was adapted to the sociocultural context of Brazilian children, and its psychometric properties were investigated for evaluating the vision-related quality of life of these individuals.
Methods: This was a nested cross-sectional epidemiological study that prospectively monitored a cohort of 142 preschool children at a single referral university hospital in Belo Horizonte, Brazil. All children underwent complete ophthalmological examination, including visual acuity testing and binocular indirect ophthalmoscopy. Questionnaires were applied to their parents and caregivers to evaluate quality of life perception, as well as socioeconomic status of their families. Psychometric properties of the quality of life scale were evaluated by multivariate statistical analyses.
Results: Adaptation to the Brazilian version of CVFQ-7 resulted in CVFQ-BR-toxo, a questionnaire for evaluating the perception of parents/caregivers about the vision-related quality of life of preschool children with congenital toxoplasmosis. The following six subscales were identified based on description, variability structure, and interpretation/grouping of items: general health, visual acuity, visual performance/functional vision, personal and social behavior, impact on family, and treatment. Children with low vision related to congenital toxoplasmosis had significantly lower scores for the following subscales: visual acuity (p=0.004), visual performance/functional vision (p=0.008), impact on family (p=0.001), and overall health (p=0.001).
Conclusion: Psychometric properties were appropriate concerning the validity of the quality of life construct. CVFQ-BR-toxo could demonstrate the impact of vision impairment on families of children with congenital toxoplasmosis.

Keywords: Quality of life; Low vision, Uveitis; Toxoplasmosis, congenital; Child

Purpose: This study aimed to compare the changes in the lacrimal functional unit in the following two models of neurogenic dry eye syndrome: sensory denervation of the cornea versus autonomic denervation of the lacrimal gland.
Methods: The neural network supports the lacrimal functional unit. It can be divided into afferent (sensory) and efferent (autonomic) pathways and is affected by severe diseases that compromise the lacrimal functional unit. Male Wistar, 8-week-old rats were divided into the following three groups: 1) control naïve (n=16 animals); 2) autonomic denervation: where rats were subjected to right lacrimal gland nerve ablation and evaluated after 1 and 2 months (1M and 2M) after the procedure (n=7 animals per subgroup, autonomic denervation 1M and autonomic denervation 2M, respectively); 3) sensory denervation induced by 0.2% benzalkonium chloride eye drops, twice a day for 7 days in the right eye (n=10 animals). The corneal sensitivity was measured using the eye wipe test with capsaicin (10 μM). The quantitative real-time PCR was performed to compare the mRNA expressions of proinflammatory cytokines, such as Il-1β, Il-6, Tnf, Mmp9, in the cornea, trigeminal ganglion, and lacrimal gland. In addition, the mRNA of the promitotic factors in the lacrimal gland, such as Bmp7, Runx1, Runx3, Fgf10, and Smad1, was compared.
Results: Sensory denervation induced corneal hyperalgesia (p=0.001). Sensory denervation and autonomic denervation increased the mRNA of proinflammatory cytokines in the cornea and lacrimal gland (p<0.05), but only sensory denervation increased the mRNA levels of Il-1β and Tnf in the trigeminal ganglion (p<0.05) compared with the control naïve.
Conclusions: Autonomic denervation and sensory denervation models can have common features, such as inflammation of different parts of the lacrimal functional unit. However, hyperesthesia and inflammatory markers in the trigeminal ganglion because of sensory denervation and the expression of regenerative mediators in the lacrimal gland owing to autonomic denervation are the distinguishing features of these diseases that can be explored in future studies assessing dry eye syndrome secondary to neural damage of the lacrimal functional unit.

Keywords: Cornea; Lacrimal functional unit; Lacrimal apparatus; Hypersensitivity; Wistar rats; Dry eye syndrome

PURPOSE: To translate and validate the Contact Lens Dry Eyes Questionnaire (CLDEQ-8) to Portuguese language and to describe the impact of soft contact lenses on the ocular surface.
METHODS: We conducted a descriptive transversal study with the aim to: (1) translate and validate the CLDEQ-8 questionnaire to Portuguese language and (2) apply the CLDEQ-8 to a group of contact lens wearers along with a broad evaluation of the impact of soft contact lens on the ocular surface. The evaluation of the impact of soft contact lens was performed for a study population of 81 subjects, categorized in two groups: Group A: 61 contact lens wearers and Group B (control): 20 noncontact lens wearers. The study exclusion criteria were rigid contact lens wear, systemic or ocular diseases, the use of medications predisposing to ocular surface damage, and previous ocular surgeries.
RESULTS: For the CLDEQ-8 questionnaire translation and validation, Kappa agreement values were ≥0.7 in all questions, implying a good agreement between the Portuguese and English language versions. Considering the ocular surface evaluation of the subjects, all parameters differed in Soft contact lens wearers when compared with the controls (p<0.05), except in those related to tear volume, such as the tear meniscus height and Schirmer test.
CONCLUSIONS: This study provided a translated and validated Portuguese version of CLDEQ-8 questionnaire, which represents an important tool for the evolution of contact lens wearers. The broad evaluation of the ocular surface revealed an association between soft contact lens wearing and ocular surface disturbances.

Keywords: Contact lens; Dry eye syndrome; Ocular surface; Survey and questionnaire; Reproducibility of results

We report the case of a 46-year-old diabetic man receiving treatment for rhino-orbital-cerebral mucormycosis with liposomal amphotericin B and surgical debridement. The patient’s condition worsened clinically, accompanied by the loss of ocular motility and a visual acuity of absence of light perception. Radiological extension of the infection was evidenced, with invasion of the cavernous sinus. Based on ophthalmological findings, exenteration (a potentially disfiguring procedure) was indicated, but we opted for wide surgical debridement and administration of amphotericin B via intraconal catheter. Clinical improvement and resolution of inflammation occurred after 2 weeks of treatment. Thus, rhino-orbital-cerebral mucormycosis was effectively controlled through intraconal administration of amphotericin B, while avoiding exenteration. The intervention should be considered as an adjuvant treatment in selected rhino-orbital-cerebral mucormycosis cases before attempting exenteration.

Keywords: Mucormycosis; Orbital cellulitis; Amphotericin B; Orbit; Fungal infections

Microscopic polyangiitis is a rare autoimmune disease of unknown etiology, characterized by inflammation and necrosis of blood vessels. It forms a part of the antineutrophil cytoplasmic antibody-associated vasculitides-a heterogeneous group of disorders characterized by vasculitis. It is a systemic disease affecting multiple organs. The patients may present with a wide variety of symptoms. Ocular manifestations may present as its initial clinical symptoms, necessitating a multidisciplinary approach for reducing the morbidity and mortality. Early diagnosis aids in the formulation of appropriate treatment and prevention of further complications. Aggressive treatment, including surgery, is often necessary to limit structural damage and preserve visual function. We present the case of an 82-year-old woman who initially presented with peripheral ulcerative keratitis that led to the diagnosis of microscopic polyangiitis.

Keywords: Corneal ulcer; Microscopic polyangiitis; Systemic vasculitis; Biological dressings; Autoimmune diseases

This is a case report of a 2-year-old male patient with cognitive delay, facial abnormalities, and microcornea in the right eye, who was referred for ophthalmological investigation. The initial ophthalmological examination revealed hypertelorism, epicanthus, nystagmus, esotropia, and microcornea in the right eye. The examination under anesthesia revealed microphthalmia in the right eye, and iris, retina, and optic nerve coloboma in both eyes. Whole exome sequencing revealed evidence of a heterozygotic pathogenic variant in PACS1. The PACS1 pathogenic variant in association with the clinical findings confirmed the diagnosis of Schuurs-Hoeijmakers syndrome. To our knowledge, this is the first report to describe microcornea and microphthalmia as additional ocular manifestations of Schuurs-Hoeijmakers syndrome.

Keywords: Microphthalmos; Optic nerve; Eye manifestation; Abnormality, Multiple/genetics; Phenotype; Syndrome; Developmental disability

The thermal effects of laser cutting machines could damage the macula. A few studies in the literature have described macular injury induced by industrial laser burns. The aim of this study was to report the clinical, visual, and optical coherence tomography findings in a gold refinery worker with laser-induced maculopathy. A 21-year-old male gold refinery worker had vision loss in his right eye after using a laser cutting machine without wearing laser eye protection gear. At the first visit (24 h later), his best-corrected visual acuity was 7/10 in the right eye and 10/10 in the left eye. The anterior segment examination was normal. In fundus examination, focal, round, and yellowish lesion was detected within the fovea. The optical coherence tomography findings were foveal outer retinal disruptions and irregularities extending from the outer plexiform layer to the retina pigment epithelium. After 4 months, the best-corrected visual acuity had improved to 1.0, and the optical coherence tomography findings had resolved.

Keywords: Maculopathy; Macular degeneration; Tomography, optical coherence; Laser

This study attempts to review whether the coronavirus disease-2019 (COVID-19) is transmitted through the ocular surface and examine the symptoms and signs of ocular disease. Considering that COVID-19 is transmitted by airborne droplets and close contact with infected individuals, we will also review the conditions to which eye clinics and ophthalmologists should pay attention to prevent the transmission of the disease. Although some researchers have argued that COVID-19 transmission cannot occur through the ocular surface, most of them are of the opinion that the ocular surface is a potential pathway of transmission. Until date, ocular signs and symptoms have been rarely reported in the COVID-19 patients. However, there are case reports of conjunctivitis as the first, and rarely, the only clinical symptom of the disease. In addition, low coronavirus RNA positivity can be detected in the ocular surface samples. Further laboratory and clinical investigations are needed to ascertain whether the ocular surface is one of the potential transmission pathways through which severe acute respiratory syndrome-coronavirus 2 can gain entry into the human body.

Keywords: Coronavirus infections; Coronavirus; COVID-19; SARS-CoV-2; Conjunctivitis; Eye manifestations; Disease transmission, infectious